Publications
(#)represents co-first and (*)represents co-corresponding/last authorship.
Representative papers
Chen Du#, Weiliang Fan, and Yu Zhou*. Integrated Biochemical and Computational Methods for Deciphering RNA-Processing Codes. WIREs RNA 15, e1875 (2024).
RNA processing involves steps such as capping, splicing, polyadenylation, modification, and nuclear export. These steps are essential for transforming genetic information in DNA into proteins and contribute to RNA diversity and complexity. Many biochemical methods have been developed to profile and quantify RNAs, as well as to identify the interactions be...
Jing Fan#*, Yimin Wang#, Miaomiao Wen#, Deng Tong#, Kai Wu, Kunming Yan, Peixuan Jia, Yi Zhu, Qinyu Liu, Hecun Zou, Peng Zhao, Falong Lu, Caihong Yun, Yuanchao Xue, Yu Zhou*, and Hong Cheng*. Dual modes of ZFC3H1 confer selectivity in nuclear RNA sorting. Molecular Cell S1097276524008232 (2024) doi:10.1016/j.molcel.2024.09.032.
The export and degradation pathways compete to sort nuclear RNAs, yet the default pathway remains unclear. Sorting of mature RNAs to degradation, facilitated by the exosome co-factor poly(A) exosome targeting (PAXT), is particularly challenging for their resemblance to mRNAs intended for translation. Here, we unveil that ZFC3H1, a core PAXT component, is ...
Peng Tang#, Jiayi Yang#, Zonggui Chen#, Chen Du, Yang Yang, Haiping Zhao, Li Huang, Guangnan Li, Feiyan Liu, Bei Dong, Ting Shan, Xichen Bao and Yu Zhou*. Nuclear retention coupled with sequential polyadenylation dictates post-transcriptional m6A modification in the nucleus. Molecular Cell, 2024, ISSN 1097-2765
N6-methyladenosine (m6A) modification is deemed to be co-transcriptionally installed on pre-mRNAs, thereby influencing various downstream RNA metabolism events. However, the causal relationship between m6A modification and RNA processing is often unclear, resulting in premature or even misleading generalizations on the function of m6A modification. Here, ...
Xinghai Yu#, Jinghua Zhou#, Wenkai Ye#, Jingxiu Xu, Rui Li, Li Huang, Yi Chai, Miaomiao Wen, Suhong Xu* & Yu Zhou*. Time-course swRNA-seq uncovers a hierarchical gene regulatory network in controlling the response-repair-remodeling after wounding. Communications Biology 7, 694 (2024). https://doi.org/10.1038/s42003-024-06352-w
Wounding initiates intricate responses crucial for tissue repair and regeneration. Yet, the gene regulatory networks governing wound healing remain poorly understood. Here, employing single-worm RNA sequencing (swRNA-seq) across 12 time-points, we delineated a three-stage wound repair process in C. elegans: response, repair, and remodeling. Integrating di...
Changshou Wang#, Lin Xu#, Chen Du#, Hao Yun#, Keyun Wang#, Hui Liu, Mingliang Ye*, Jing Fan*, Yu Zhou* and Hong Cheng*. CDK11 requires a critical activator SAP30BP to regulate pre‐mRNA splicing. EMBO J (2023)42: e114051. https://doi.org/10.15252/embj.2023114051
CDK11 is an emerging druggable target for cancer therapy due to its prevalent roles in phosphorylating critical transcription and splicing factors and in facilitating cell cycle progression in cancer cells. Like other cyclin‐dependent kinases, CDK11 requires its cognate cyclin, cyclin L1 or cyclin L2, for activation. However, little is known about how CDK...
Ting Shan#, Feiyan Liu#, Miaomiao Wen#, Zonggui Chen, Shaopeng Li, Yafen Wang, Hong Cheng, Yu Zhou*. m6A modification negatively regulates translation by switching mRNA from polysome to P-body via IGF2BP3. Molecular Cell S1097276523009115 (2023) doi:10.1016/j.molcel.2023.10.040.
In the cytoplasm, mRNAs are dynamically partitioned into translating and non-translating pools, but the mechanism for this regulation has largely remained elusive. Here, we report that m6A regulates mRNA partitioning between polysome and P-body where a pool of non-translating mRNAs resides. By quantifying the m6A level of polysomal and cytoplasmic mRNAs w...
Li Huang#, Guangnan Li#, Chen Du#, Yu Jia, Jiayi Yang, Weiliang Fan, Yong-Zhen Xu, Hong Cheng & Yu Zhou*. The polyA tail facilitates splicing of last introns with weak 3′ splice sites via PABPN1. EMBO reports, e5718 (2023).
The polyA tail of mRNAs is important for many aspects of RNA metabolism. However, whether and how it regulates pre‐mRNA splicing is still unknown. Here, we report that the polyA tail acts as a splicing enhancer for the last intron via the nuclear polyA binding protein PABPN1 in HeLa cells. PABPN1‐depletion induces the retention of a group of introns with ...
Dehe Wang#, Xiao Hu#, Hanzhe Ye, Yue Wang, Qian Yang, Xiaodong Liang, Zilin Wang, Yifan Zhou, Miaomiao Wen, Xueyan Yuan, Xiaomin Zheng, Wen Ye, Boyu Guo, Mayila Yusuyin, Eugenia Russinova, Yu Zhou* & Kun Wang*. Cell-specific clock-controlled gene expression program regulates rhythmic fiber cell growth in cotton. Genome Biology, 24, Article number: 49 (2023). doi: 10.1186/s13059-023-02886-0
Background The epidermis of cotton ovule produces fibers, the most important natural cellulose source for the global textile industry. However, the molecular mechanism of fiber cell growth is still poorly understood. Results Here, we develop an optimized protoplasting method, and integrate single-cell RNA sequencing (scRNA-seq) and single-cell ATAC seq...
Guangnan Li#, Zhidong Tang#, Weiliang Fan#, Xi Wang#, Li Huang, Yu Jia, Manli Wang, Zhihong Hu, Yu Zhou*. Atlas of interactions between SARS-CoV-2 macromolecules and host proteins. Cell Insight, Volume 2, Issue 1, February 2023, 100068. doi: 10.1016/j.cellin.2022.100068
The proteins and RNAs of viruses extensively interact with host proteins after infection. We collected and reanalyzed all available datasets of protein-protein and RNA-protein interactions related to SARS-CoV-2. We investigated the reproducibility of those interactions and made strict filters to identify highly confident interactions. We systematically an...
Kai Wu#, Dehe Wang#, Junhao Wang, Yu Zhou*. Translation landscape of SARS-CoV-2 noncanonical subgenomic RNAs. Virologica Sinica, 37(6), 813–822. https://doi.org/10.1016/j.virs.2022.09.003
The ongoing COVID-19 pandemic is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with a positive-stranded RNA genome. Current proteomic studies of SARS-CoV-2 mainly focus on the proteins encoded by its genomic RNA (gRNA) or canonical subgenomic RNAs (sgRNAs). Here, we systematically investigated the translation landscape of SARS-CoV...
Peng Tang# & Yu Zhou*. Alternative polyadenylation regulation: insights from sequential polyadenylation. Transcription, Volume 13, 2022 - Issue 4-5. doi: 10.1080/21541264.2022.2114776
The processing of the proximal and distal poly(A) sites in alternative polyadenylation (APA) has long been thought to independently occur on pre-mRNAs during transcription. However, a recent study by our groups demonstrated that the proximal sites for many genes could be activated sequentially following the distal ones, suggesting a multi-cleavage-same-tr...
Bingbing Xu#, Yanda Zhu#, Changchang Cao#, Hao Chen#, Qiongli Jin#, Guangnan Li#, Junfeng Ma#, Siwy Ling Yang#, Jieyu Zhao#, Jianghui Zhu#, Yiliang Ding*, Xianyang Fang*, Yongfeng Jin*, Chun Kit Kwok*, Aiming Ren*, Yue Wan*, Zhiye Wang*, Yuanchao Xue*, Huakun Zhang*, Qiangfeng Cliff Zhang* & Yu Zhou*. Recent advances in RNA structurome. Science China Life Sciences, volume 65, pages1285–1324 (2022). doi: 10.1007/s11427-021-2116-2
RNA structures are essential to support RNA functions and regulation in various biological processes. Recently, a range of novel technologies have been developed to decode genome-wide RNA structures and novel modes of functionality across a wide range of species. In this review, we summarize key strategies for probing the RNA structurome and discuss the p...
Shaopeng Li#, Linmao Li#, Weiliang Fan, Suping Ma, Cheng Zhang, Jang Chol Kim, Kun Wang, Eugenia Russinova, Yuxian Zhu, and Yu Zhou*. LeafNet: a tool for segmenting and quantifying stomata and pavement cells. The Plant Cell, DOI:10.1093/plcell/koac021, January 2022.
Stomata play important roles in gas and water exchange in leaves. The morphological features of stomata and pavement cells are highly plastic and are regulated during development. However, it is very laborious and time-consuming to collect accurate quantitative data from the leaf surface by manual phenotyping. Here, we introduce LeafNet, a tool that autom...
Geng Chen#, Yang Yang#, Qi-Jia Wu#, Liu Cao#, Wen Ruan, Changwei Shao, Li Jiang, Peng Tang, Suping Ma, Ao Jiang, Zhen Wang, Kai Wu, Qiangfeng Cliff Zhang, Xiang-Dong Fu, and Yu Zhou*. ILF3 represses repeat-derived microRNAs targeting RIG-I mediated type I interferon response. Journal of Molecular Biology, DOI:10.1016/j.jmb.2022.167469, February 2022.
MicroRNAs (miRNAs) play important roles in regulated gene expression and miRNA biogenesis is also subject to regulation, together constituting critical regulatory circuitries in numerous physiological and pathological processes. As a dsRNA binding protein, interleukin enhancer binding factor 3 (ILF3) has been implicated as a negative regulator in miRNA bi...
Peng Tang#, Yang Yang#, Guangnan Li, Li Huang, Miaomiao Wen, Wen Ruan, Xiaolong Guo, Chen Zhang, Xinxin Zuo, Daji Luo, Yongzhen Xu, Xiang-Dong Fu*, and Yu Zhou*. Alternative polyadenylation by sequential activation of distal and proximal PolyA sites. Nat Struct Mol Biol, 29(1):21–31, January 2022.
Analogous to alternative splicing, alternative polyadenylation (APA) has long been thought to occur independently at proximal and distal polyA sites. Using fractionation-seq, we unexpectedly identified several hundred APA genes in human cells whose distal polyA isoforms are retained in chromatin/nuclear matrix and whose proximal polyA isoforms are release...
Yangyang Li#, Zonggui Chen#, Hairong Liu#, Qiming Li, Xing Lin, Shuhui Ji, Rui Li, Shaopeng Li, Weiliang Fan, Haiping Zhao, Zuoyan Zhu, Wei Hu*, Yu Zhou*, and Daji Luo*. ASER: Animal Sex Reversal Database. Genomics, Proteomics & Bioinformatics, DOI:10.1016/j.gpb.2021.10.001, November 2021.
Sex reversal, representing an extraordinary sexual plasticity during the life cycle, not only triggers reproduction in animals but also affects reproductive and endocrine system-related diseases and cancers in humans. Sex reversal has been broadly reported in animals, however, an integrated resource hub of sex reversal information is still lacking. Here, ...
Zhidong Tang#, Weiliang Fan#, Qiming Li#, Dehe Wang, Miaomiao Wen, Junhao Wang, Xingqiao Li, and Yu Zhou*. MVIP: multi-omics portal of viral infection. Nucleic Acids Research, 50(D1):D817–D827, January 2022.
Virus infections are huge threats to living organisms and cause many diseases, such as COVID-19 caused by SARS-CoV-2, which has led to millions of deaths. To develop effective strategies to control viral infection, we need to understand its molecular events in host cells. Virus related functional genomic datasets are growing rapidly, however, an integrati...
Jiaqi Xia#, Peng Bai#, Weiliang Fan, Qiming Li, Yongzheng Li, Dehe Wang, Lei Yin*, and Yu Zhou*. NEPdb: A Database of T-Cell Experimentally-Validated Neoantigens and Pan-Cancer Predicted Neoepitopes for Cancer Immunotherapy. Front Immunol, 2021, 12:644637
T-cell recognition of somatic mutation-derived cancer neoepitopes can lead to tumor regression. Due to the difficulty to identify effective neoepitopes, constructing a database for sharing experimentally validated cancer neoantigens will be beneficial to precise cancer immunotherapy. Meanwhile, the routine neoepitope prediction in silico is important but ...
Dehe Wang#, Ao Jiang#, Jiangpeng Feng#, Guangnan Li#, Dong Guo#, Muhammad Sajid, Kai Wu, Qiuhan Zhang, Yann Ponty, Sebastian Will, Feiyan Liu, Xinghai Yu, Shaopeng Li, Qianyun Liu, Xing-Lou Yang, Ming Guo, Xingqiao Li, Mingzhou Chen, Zheng-Li Shi, Ke Lan*, Yu Chen*, and Yu Zhou*. The SARS-CoV-2 Subgenome Landscape and Its Novel Regulatory Features. Molecular Cell. available online Mar. 2021.
Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is currently a global pandemic. CoVs are known to generate negative subgenomes (subgenomic RNAs [sgRNAs]) through transcription-regulating sequence (TRS)-dependent template switching, but the global dynamic landscapes of coronaviral subgenomes and ...
Xinxin Zuo#, Jie Zhou#, Yinming Li#, Kai Wu, Zonggui Chen, Zhiwei Luo, Xiaorong Zhang, Yi Liang, Miguel A. Esteban, Yu Zhou*, and Xiang-Dong Fu*. 2021. TDP-43 Aggregation Induced by Oxidative Stress Causes Global Mitochondrial Imbalance in ALS. Nature Structural & Molecular Biology, 28(2):132–42.
Amyotrophic lateral sclerosis (ALS) was initially thought to be associated with oxidative stress when it was first linked to mutant superoxide dismutase 1 (SOD1). The subsequent discovery of ALS-linked genes functioning in RNA processing and proteostasis raised the question of how different biological pathways converge to cause the disease. Both familial ...
Yong Xiong#, Yuan Liu#, Liu Cao#, Dehe Wang#, Ming Guo, Ao Jiang, Dong Guo, Wenjia Hu, Jiayi Yang, Zhidong Tang, Honglong Wu, Yongquan Lin, Meiyuan Zhang, Qi Zhang, Mang Shi, Yingle Liu, Yu Zhou*, Ke Lan*, and Yu Chen*. Transcriptomic characteristics of bronchoalveolar lavage fluid and peripheral blood mononuclear cells in COVID-19 patients. Emerging Microbes & Infections, 9(1):761–770, January 2020.
Circulating in China and 158 other countries and areas, the ongoing COVID-19 outbreak has caused devastating mortality and posed a great threat to public health. However, efforts to identify effectively supportive therapeutic drugs and treatments has been hampered by our limited understanding of host immune response for this fatal disease. To characterize...
Peng Dai#, Xin Wang#, Lan-Tao Gou#, Zhi-Tong Li#, Ze Wen#, Zong-Gui Chen#, Min-Min Hua, Ai Zhong, Lingbo Wang, Haiyang Su, Huida Wan, Kun Qian, Lujian Liao, Jinsong Li, Bin Tian, Dangsheng Li, Xiang-Dong Fu, Hui-Juan Shi*, Yu Zhou*, and Mo-Fang Liu*. A Translation-Activating Function of MIWI/piRNA during Mouse Spermiogenesis. Cell, 179(7):1566–1581.e16, December 2019.
Spermiogenesis is a highly orchestrated developmental process during which chromatin condensation decouples transcription from translation. Spermiogenic mRNAs are transcribed earlier and stored in a translationally inert state until needed for translation; however, it remains largely unclear how such repressed mRNAs become activated during spermiogenesis....
Dehe Wang#, Weiliang Fan#, Xiaolong Guo#, Kai Wu, Siyu Zhou, Zonggui Chen, Danyang Li, Kun Wang*, Yuxian Zhu*, and Yu Zhou*. MaGenDB: a functional genomics hub for Malvaceae plants. Nucleic Acids Research, pages gkz953, January 2020.
Malvaceae is a family of flowering plants containing many economically important plant species including cotton, cacao and durian. Recently, the genomes of several Malvaceae species have been decoded, and many omics data were generated for individual species. However, no integrative database of multiple species, enabling users to jointly compare and analy...
Kun Wang#, Dehe Wang#, Xiaomin Zheng, Ai Qin, Jie Zhou, Boyu Guo, Yanjun Chen, Xingpeng Wen, Wen Ye, Yu Zhou*, and Yuxian Zhu*. Multi-strategic RNA-seq analysis reveals a high-resolution transcriptional landscape in cotton. Nature Communications, 10(1):4714, December 2019.
Cotton is an important natural fiber crop, however, its comprehensive and high-resolution gene map is lacking. Here we integrate four complementary high-throughput techniques, including Pacbio long read Iso-seq, strand-specific RNA-seq, CAGE-seq, and PolyA-seq, to systematically explore the transcription landscape across 16 tissues or different organ type...
Jianshu Wang#, Jiyun Chen#, Guifen Wu#, Hongling Zhang#, Xian Du#, Suli Chen, Li Zhang, Ke Wang, Jing Fan, Shuaixin Gao, Xudong Wu, Shouxiang Zhang, Bin Kuai, Peng Zhao, Binkai Chi, Lantian Wang, Guohui Li, Catherine C.L. Wong, Yu Zhou*, Jinsong Li*, Caihong Yun*, and Hong Cheng*. NRDE2 negatively regulates exosome functions by inhibiting MTR4 recruitment and exosome interaction. Genes & Development, March 2019.
The exosome functions in the degradation of diverse RNA species, yet how it is negatively regulated remains largely unknown. Here, we show that NRDE2 forms a 1:1 complex with MTR4, a nuclear exosome cofactor critical for exosome recruitment, via a conserved MTR4-interacting domain (MID). Unexpectedly, NRDE2 mainly localizes in nuclear speckles, where it i...
Kai Zhang#, Xiaorong Zhang#, Zhiqiang Cai#, Jie Zhou#, Ran Cao, Ya Zhao, Zonggui Chen, Dehe Wang, Wen Ruan, Qian Zhao, Guangqiao Liu, Yuanchao Xue, Yan Qin, Bing Zhou, Ligang Wu, Timothy Nilsen, Yu Zhou*, and Xiang-Dong Fu*. A novel class of microRNA-recognition elements that function only within open reading frames.
MicroRNAs (miRNAs) are well known to target 3′ untranslated regions (3′ UTRs) in mRNAs, thereby silencing gene expression at the post-transcriptional level. Multiple reports have also indicated the ability of miRNAs to target protein-coding sequences (CDS); however, miRNAs have been generally believed to function through similar mechanisms regardless of t...
Jiaqi Gu#, Ming Wang#, Yang Yang#, Ding Qiu, Yiqun Zhang, Jinbiao Ma*, Yu Zhou*, Gregory J. Hannon*, and Yang Yu*. GoldCLIP: Gel-omitted Ligation-dependent CLIP. Genomics, Proteomics & Bioinformatics, 16(2):136–143, April 2018.
Protein–RNA interaction networks are essential to understand gene regulation control. Identifying binding sites of RNA-binding proteins (RBPs) by the UV-crosslinking and immunoprecipitation (CLIP) represents one of the most powerful methods to map protein–RNA interactions in vivo. However, the traditional CLIP protocol is technically challenging, which re...
Huiwu Ouyang, Kai Zhang, Kristi Fox-Walsh, Yang Yang, Chen Zhang, Jie Huang, Hairi Li, Yu Zhou*, and Xiang-Dong Fu*. The RNA binding protein EWS is broadly involved in the regulation of pri-miRNA processing in mammalian cells. Nucleic Acids Research, 45(21):12481–12495, December 2017.
The Ewing Sarcoma protein (EWS) is a multifaceted RNA binding protein (RBP) with established roles in transcription, pre-mRNA processing and DNA damage response. By generating high quality EWS-RNA interactome, we uncovered its specific and prevalent interaction with a large subset of primary microRNAs (pri-miRNAs) in mammalian cells. Knockdown of EWS redu...
Li Jiang#, Changwei Shao#, Qi-Jia Wu#, Geng Chen, Jie Zhou, Bo Yang, Hairi Li, Lan-Tao Gou, Yi Zhang, Yangming Wang, Gene W Yeo, Yu Zhou*, and Xiang-Dong Fu*. NEAT1 scaffolds RNA-binding proteins and the Microprocessor to globally enhance pri-miRNA processing. Nature Structural & Molecular Biology, 24:816–824, August 2017.
MicroRNA (miRNA) biogenesis is known to be modulated by a variety of RNA-binding proteins (RBPs), but in most cases, individual RBPs appear to influence the processing of a small subset of target miRNAs. Here, we report that the RNA-binding NONO-PSF heterodimer binds a large number of expressed pri-miRNAs in HeLa cells to globally enhance pri-miRNA proces...
Chaoliang Wei#, Rui Xiao#, Liang Chen#, Hanwei Cui#, Yu Zhou#, Yuanchao Xue, Jing Hu, Bing Zhou, Taiki Tsutsui, Jinsong Qiu, Hairi Li, Liling Tang, and Xiang-Dong Fu*. RBFox2 Binds Nascent RNA to Globally Regulate Polycomb Complex 2 Targeting in Mammalian Genomes. Molecular Cell, 62(6):875–889, May 2016.
Increasing evidence suggests that diverse RNA binding proteins (RBPs) interact with regulatory RNAs to regulate transcription. RBFox2 is a well-characterized pre-mRNA splicing regulator, but we now encounter an unexpected paradigm where depletion of this RBP induces widespread increase in nascent RNA production in diverse cell types. Chromatin immunopreci...
Lanfeng Wang#, Yu Zhou#, Liang Xu#, Rui Xiao#, Xingyu Lu, Liang Chen, Jenny Chong, Hairi Li, Chuan He, Xiang-Dong Fu*, and Dong Wang*. Molecular basis for 5-carboxycytosine recognition by RNA polymerase II elongation complex. Nature, 523(7562):621–625, June 2015.
DNA methylation at selective cytosine residues (5-methylcytosine (5mC)) and their removal by TET-mediated DNA demethylation are critical for setting up pluripotent states in early embryonic development1,2. TET enzymes successively convert 5mC to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC), with 5fC and 5caC subjec...
Yu Zhou#, Hai-Ri Li, Jie Huang, Ge Jin, and Xiang-Dong Fu*. Multiplex analysis of polyA-linked sequences (MAPS): an RNA-seq strategy to profile poly(A+) RNA. Methods in Molecular Biology, 1125:169–178, February 2014.
We summarize 12 experimental methods that have been developed for profiling gene expression by focusing on the 3'-end of poly(A+) mRNA, distilling both common and unique features. Of this family of methods, we provide detailed protocol for MAPS, a method we believe is the simplest and most cost-effective for profiling gene expression and quantifying alter...
Yu Zhou#, Yann Ponty#, Stéphane Vialette, Jérôme Waldispühl, Yi Zhang, and Alain Denise*. Flexible RNA design under structure and sequence constraints using formal languages. BCB'13: Proceedings of the International Conference on Bioinformatics, Computational Biology and Biomedical Informatics, September 2013 Pages 229–238. doi: 10.1145/2506583.2506623
The problem of RNA secondary structure design is the following: given a target secondary structure, one aims to create a sequence that folds into, or is compatible with, a given structure. In several practical applications in biology, additional constraints must be taken into account, such as the presence/absence of regulatory motifs, either at a specific...
Shatakshi Pandit#, Yu Zhou#, Lily Shiue#, Gabriela Coutinho-Mansfield, Hairi Li, Jinsong Qiu, Jie Huang, Gene W. Yeo, Manuel Ares*, and Xiang-Dong Fu*. Genome-wide Analysis Reveals SR Protein Cooperation and Competition in Regulated Splicing. Molecular Cell, 50(2):223–235, April 2013.
SR proteins are well-characterized RNA binding proteins that promote exon inclusion by binding to exonic splicing enhancers (ESEs). However, it has been unclear whether regulatory rules deduced on model genes apply generally to activities of SR proteins in the cell. Here, we report global analyses of two prototypical SR proteins, SRSF1 (SF2/ASF) and SRSF2...
Yuanchao Xue#, Yu Zhou#, Tongbin Wu, Tuo Zhu, Xiong Ji, Young-Soo Kwon, Chao Zhang, Gene Yeo, Douglas L. Black, Hui Sun, Xiang-Dong Fu*, and Yi Zhang*. Genome-wide Analysis of PTB-RNA Interactions Reveals a Strategy Used by the General Splicing Repressor to Modulate Exon Inclusion or Skipping. Molecular Cell, 36(6):996–1006, December 2009.
Recent transcriptome analysis indicates that > 90% of human genes undergo alternative splicing, underscoring the contribution of differential RNA processing to diverse proteomes in higher eukaryotic cells. The polypyrimidine tract-binding protein PTB is a well-characterized splicing repressor, but PTB knockdown causes both exon inclusion and skipping. Gen...
Yu Zhou#, Chen Lu#, Qi-Jia Wu#, Yu Wang, Zhi-Tao Sun, Jia-Cong Deng, and Yi Zhang*. GISSD: Group I Intron Sequence and Structure Database. Nucleic Acids Research, 36(Database issue):D31–37, January 2008.
Group I Intron Sequence and Structure Database (GISSD) is a specialized and comprehensive database for group I introns, focusing on the integration of useful group I intron information from available databases and providing de novo data that is essential for understanding these introns at a systematic level. This database presents 1789 complete intron rec...
Co-author papers
Hongyun Wang#, Jiangpeng Feng, Cong Zeng, Jiejie Liu, Zhiying Fu, Dehe Wang, Yafen Wang, Lu Zhang, Jiali Li, Ao Jiang, Miao He, Yuanyuan Cao, Kun Yan, Hao Tang, Deyin Guo, Ke Xu, Xiang Zhou, Li Zhou, Ke Lan, Yu Zhou & Yu Chen*. NSUN2-mediated M5c methylation of IRF3 mRNA negatively regulates type I interferon responses during various viral infections. Emerging microbes & infections, 12(1), 2178238. doi: 10.1080/22221751.2023.2178238
5-Methylcytosine (m5C) is a widespread post-transcriptional RNA modification and is reported to be involved in manifold cellular responses and biological processes through regulating RNA metabolism. However, its regulatory role in antiviral innate immunity has not yet been elucidated. Here, we report that NSUN2, a typical m5C methyltransferase, negatively...
Yongliang Zhao#, Wenjia Ni#, Simeng Liang#, Lianghui Dong#, Min Xiang#, Zeng Cai#, Danping Niu#, Qiuhan Zhang, Dehe Wang, Yucheng Zheng, Zhen Zhang, Dan Zhou, Wenhua Guo, Yongbing Pan, Xiaoli Wu, Yimin Yang, Zhaofei Jing, Yongzhong Jiang, Yu Chen, Huan Yan, Yu Zhou, Ke Xu* & Ke Lan*. Vaccination with Span, an antigen guided by SARS-CoV-2 S protein evolution, protects against challenge with viral variants in mice. Science translational medicine, 15(677), eabo3332. doi: 10.1126/scitranslmed.abo3332
SARS-CoV-2 continues to accumulate mutations to evade immunity, leading to breakthrough infections after vaccination. How researchers can anticipate the evolutionary trajectory of the virus in advance in the design of next-generation vaccines requires investigation. Here, we performed a comprehensive study of 11,650,487 SARS-CoV-2 sequences, which reveale...
Jun-Yan Kang#, Ze Wen#, Duo Pan#, Yuhan Zhang#, Qing Li#, Ai Zhong#, Xinghai Yu#, Yi-Chen Wu, Yu Chen, Xiangzheng Zhang, Peng-Cheng Kou, Junlan Geng, Ying-Yi Wang, Min-Min Hua, Ruiting Zong, Biao Li, Hui-Juan Shi, Dangsheng Li, Xiang-Dong Fu, Jinsong Li, David L Nelson, Xuejiang Guo, Yu Zhou, Lan-Tao Gou, Ying Huang*, Mo-Fang Liu*. LLPS of FXR1 drives spermiogenesis by activating translation of stored mRNAs. Science. 2022 Aug 12;377(6607):eabj6647. doi: 10.1126/science.abj6647. Epub 2022 Aug 12.
Postmeiotic spermatids use a unique strategy to coordinate gene expression with morphological transformation, in which transcription and translation take place at separate developmental stages, but how mRNAs stored as translationally inert messenger ribonucleoproteins in developing spermatids become activated remains largely unknown. Here, we report that ...
Bo Xu#, Can Zhang, Ao Jiang, Xianhong Zhang, Fenfei Liang, Xueqing Wang, Danni Li, Chenglong Liu, Xiaomei Liu, Jing Xia, Yang Li, Yirong Wang, Zelan Yang, Jia Chen, Yu Zhou, Liang Chen* & Hui Sun*. Histone methyltransferase Dot1L recruits O-GlcNAc transferase to target chromatin sites to regulate histone O-GlcNAcylation. The Journal of biological chemistry, 298(7), 102115. https://doi.org/10.1016/j.jbc.2022.102115
O-GlcNAc transferase (OGT) is the distinctive enzyme responsible for catalyzing O-GlcNAc addition to the serine or threonine residues of thousands of cytoplasmic and nuclear proteins involved in such basic cellular processes as DNA damage repair, RNA splicing, and transcription preinitiation and initiation complex assembly. However, the molecular mechanis...
Dong Guo#, Xinghai Yu, Dan Wang, Zhifei Li, Yu Zhou, Guodong Xu, Bing Yuan, Yali Qin*, Mingzhou Chen*. SLC35B2 Acts in a Dual Role in the Host Sulfation Required for EV71 Infection. Journal of virology, 96(9), e0204221. doi: 10.1128/jvi.02042-21
As an important neurotropic enterovirus, enterovirus 71 (EV71) is occasionally associated with severe neurological diseases and high mortality rates in infants and young children. Understanding the interaction between host factors and EV71 will play a vital role in developing antivirals and optimizing vaccines. Here, we performed a genome-wide CRISPR-Cas9...
Rui Xiao, Jia-Yu Chen, Zhengyu Liang, Daji Luo, Geng Chen, Zhi John Lu, Yang Chen, Bing Zhou, Hairi Li, Xian Du, Yang Yang, Mingkui San, Xintao Wei, Wen Liu, Eric Lécuyer, Brenton R. Graveley, Gene W. Yeo, Christopher B. Burge, Michael Q. Zhang, Yu Zhou, and Xiang-Dong Fu*. Pervasive Chromatin-RNA Binding Protein Interactions Enable RNA-Based Regulation of Transcription. Cell, 178(1):107–121.e18, June 2019.
Increasing evidence suggests that transcriptional control and chromatin activities at large involve regulatory RNAs, which likely enlist specific RNA-binding proteins (RBPs). Although multiple RBPs have been implicated in transcription control, it has remained unclear how extensively RBPs directly act on chromatin. We embarked on a large-scale RBP ChIP-se...
Bing Zhou, Xiao Li, Daji Luo, Do-Hwan Lim, Yu Zhou, and Xiang-Dong Fu*. GRID-seq for comprehensive analysis of global RNA–chromatin interactions. Nature Protocols, 14(7):2036–2068, July 2019.
Chromatin in higher eukaryotic nuclei is extensively bound by various RNA species. We recently developed a method for in situ capture of global RNA interactions with DNA by deep sequencing (GRID-seq) of fixed permeabilized nuclei that allows identification of the entire repertoire of chromatin-associated RNAs in an unbiased manner. The experimental design...
Ke Wang, Changping Yin, Xian Du, Suli Chen, Jianshu Wang, Li Zhang, Lantian Wang, Yong Yu, Binkai Chi, Min Shi, Changshou Wang, Robin Reed, Yu Zhou, Jing Huang, and Hong Cheng*. A U2-snRNP–independent role of SF3b in promoting mRNA export. Proceedings of the National Academy of Sciences, 116(16):7837–7846, April 2019.
To ensure efficient and accurate gene expression, pre-mRNA processing and mRNA export need to be balanced. However, how this balance is ensured remains largely unclear. Here, we found that SF3b, a component of U2 snRNP that participates in splicing and 3′ processing of pre-mRNAs, interacts with the key mRNA export adaptor THO in vivo and in vitro. Depleti...
Jing Fan, Ke Wang, Xian Du, Jianshu Wang, Suli Chen, Yimin Wang, Min Shi, Li Zhang, Xudong Wu, Dinghai Zheng, Changshou Wang, Lantian Wang, Bin Tian, Guohui Li, Yu Zhou, and Hong Cheng*. ALYREF links 3′‐end processing to nuclear export of non‐polyadenylated mRNAs. The EMBO Journal, pages e99910, March 2019.
Synopsis The RNA-binding protein ALYREF functions in coupling nuclear export and 3'-end processing of polyadenylated mRNAs. New data identify a parallel mechanism for ALYREF also linking 3'-end processing to nuclear export of non-polyadenylated, replication-dependent histone mRNAs. ALYREF prevalently binds to a 3' region of histone mRNAs in an SLBP-depend...
Yafen Wang, Chaoxing Liu, Fan Wu, Xiong Zhang, Sheng Liu, Zonggui Chen, Weiwu Zeng, Wei Yang, Xiaolian Zhang, Yu Zhou, Xiaocheng Weng, Zhiguo Wu, and Xiang Zhou*. Highly Selective 5-Formyluracil Labeling and Genome-wide Mapping Using (2-Benzimidazolyl)Acetonitrile Probe. iScience, 9:423–432, November 2018.
Chemical modifications to nucleobases have a great influence on various cellular processes, by making gene regulation more complex, thus indicating their profound impact on aspects of heredity, growth, and disease. Here, we provide the first genome-wide map of 5-formyluracil (5fU)in living tissues and evaluate the potential roles for 5fU in genomics. We s...
Hexiu Su, Juncheng Hu, Liang Huang, Yang Yang, Morgan Thenoz, Anna Kuchmiy, Yufeng Hu, Peng Li, Hui Feng, Yu Zhou, Tom Taghon, Pieter Van Vlierberghe, Guoliang Qing, Zhichao Chen*, and Hudan Liu*. SHQ1 regulation of RNA splicing is required for T-lymphoblastic leukemia cell survival. Nature Communications, 9:4281, December 2018.
T-acute lymphoblastic leukemia (T-ALL) is an aggressive hematologic malignancy with complicated heterogeneity. Although expression profiling reveals common elevated genes in distinct T-ALL subtypes, little is known about their functional role(s) and regulatory mechanism(s). We here show that SHQ1, an H/ACA snoRNP assembly factor involved in snRNA pseudour...
Tingting Hong#, Yushu Yuan#, Zonggui Chen, Kun Xi, Tianlu Wang, Yalun Xie, Zhiyong He, Haomiao Su, Yu Zhou, Zhi-Jie Tan, Xiaocheng Weng*, and Xiang Zhou*. Precise Antibody-Independent m6A Identification via 4SedTTP-Involved and FTO-Assisted Strategy at Single-Nucleotide Resolution. Journal of the American Chemical Society, 140(18):5886–5889, May 2018.
Innovative detection techniques to achieve precise m6A distribution within mammalian transcriptome can advance our understanding of its biological functions. We specifically introduced the atom-specific replacement of oxygen with progressively larger atoms (sulfur and selenium) at 4-position of deoxythymidine triphosphate to weaken its ability to base pai...
Liang Chen#, Jia-Yu Chen#, Yi-Jou Huang#, Ying Gu, Jinsong Qiu, Hao Qian, Changwei Shao, Xuan Zhang, Jing Hu, Hairi Li, Shunmin He, Yu Zhou, Omar Abdel-Wahab, Dong-Er Zhang*, and Xiang-Dong Fu*. The Augmented R-Loop Is a Unifying Mechanism for Myelodysplastic Syndromes Induced by High-Risk Splicing Factor Mutations. Molecular Cell, 69(3):412–425.e6, February 2018.
Mutations in several general pre-mRNA splicing factors have been linked to myelodysplastic syndromes (MDSs) and solid tumors. These mutations have generally been assumed to cause disease by the resultant splicing defects, but different mutations appear to induce distinct splicing defects, raising the possibility that an alternative common mechanism is inv...
Liang Chen#, Jia-Yu Chen#, Xuan Zhang, Ying Gu, Rui Xiao, Changwei Shao, Peng Tang, Hao Qian, Daji Luo, Hairi Li, Yu Zhou, Dong-Er Zhang, and Xiang-Dong Fu*. R-ChIP Using Inactive RNase H Reveals Dynamic Coupling of R-loops with Transcriptional Pausing at Gene Promoters. Molecular Cell, 68(4):745–757.e5, November 2017.
R-loop, a three-stranded RNA/DNA structure, has been linked to induced genome instability and regulated gene expression. To enable precision analysis of R-loops in vivo, we develop an RNase-H-based approach; this reveals predominant R-loop formation near gene promoters with strong G/C skew and propensity to form G-quadruplex in non-template DNA, corrobora...
Jinsong Qiu#, Bing Zhou#, Felicitas Thol, Yu Zhou, Liang Chen, Changwei Shao, Christopher DeBoever, Jiayi Hou, Hairi Li, Anuhar Chaturvedi, Arnold Ganser, Rafael Bejar, Dong-Er Zhang*, Xiang-Dong Fu*, and Michael Heuser*. Distinct splicing signatures affect converged pathways in myelodysplastic syndrome patients carrying mutations in different splicing regulators. RNA, 22(10):1535–1549, October 2016.
Myelodysplastic syndromes (MDS) are heterogeneous myeloid disorders with prevalent mutations in several splicing factors, but the splicing programs linked to specific mutations or MDS in general remain to be systematically defined. We applied RASL-seq, a sensitive and cost-effective platform, to interrogate 5502 annotated splicing events in 169 samples fr...
Lizhen Chen, Zhijie Liu, Bing Zhou, Chaoliang Wei, Yu Zhou, Michael G Rosenfeld, Xiang-Dong Fu, Andrew D Chisholm*, and Yishi Jin*. CELF RNA binding proteins promote axon regeneration in C. elegans and mammals through alternative splicing of Syntaxins. eLife, 5:e16072, June 2016.
Axon injury triggers dramatic changes in gene expression. While transcriptional regulation of injury-induced gene expression is widely studied, less is known about the roles of RNA binding proteins (RBPs) in post-transcriptional regulation during axon regeneration. In C. elegans the CELF (CUGBP and Etr-3 Like Factor) family RBP UNC-75 is required for axon...
Yuanchao Xue*, Hao Qian, Jing Hu, Bing Zhou, Yu Zhou, Xihao Hu, Aziz Karakhanyan, Zhiping Pang, and Xiang-Dong Fu*. Sequential regulatory loops as key gatekeepers for neuronal reprogramming in human cells. Nature Neuroscience, 19(6):807–815, June 2016.
Direct conversion of somatic cells into neurons holds great promise for regenerative medicine. However, neuronal conversion is relatively inefficient in human cells compared to mouse cells. It has been unclear what might be the key barriers to reprogramming in human cells. We recently elucidated an RNA program mediated by the polypyrimidine tract binding ...
Jelena Scekic‐Zahirovic, Oliver Sendscheid, Hajer El Oussini, Mélanie Jambeau, Ying Sun, Sina Mersmann, Marina Wagner, Stéphane Dieterlé, Jérome Sinniger, Sylvie Dirrig‐Grosch, Kevin Drenner, Marie‐Christine Birling, Jinsong Qiu, Yu Zhou, Hairi Li, Xiang‐Dong Fu, Caroline Rouaux, Tatyana Shelkovnikova, Anke Witting, Albert C Ludolph, Friedemann Kiefer, Erik Storkebaum*, Clotilde Lagier‐Tourenne*, and Luc Dupuis*. Toxic gain of function from mutant FUS protein is crucial to trigger cell autonomous motor neuron loss. The EMBO Journal, 35(10):1077–1097, May 2016.
FUS is an RNA-binding protein involved in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Cytoplasmic FUS-containing aggregates are often associated with concomitant loss of nuclear FUS. Whether loss of nuclear FUS function, gain of a cytoplasmic function, or a combination of both lead to neurodegeneration remains elusive. To addres...
Chen Gao, Shuxun Ren, Jae-Hyung Lee, Jinsong Qiu, Douglas J. Chapski, Christoph D. Rau, Yu Zhou, Maha Abdellatif, Astushi Nakano, Thomas M. Vondriska, Xinshu Xiao, Xiang-Dong Fu, Jau-Nian Chen, and Yibin Wang*. RBFox1-mediated RNA splicing regulates cardiac hypertrophy and heart failure. Journal of Clinical Investigation, 126(1):195–206, November 2015.
RNA splicing is a major contributor to total transcriptome complexity; however, the functional role and regulation of splicing in heart failure remain poorly understood. Here, we used a total transcriptome profiling and bioinformatic analysis approach and identified a muscle-specific isoform of an RNA splicing regulator, RBFox1 (also known as A2BP1), as a...
Fei Chen, Yu Zhou, Yingchuan B. Qi, Vishal Khivansara, Hairi Li, Sang Young Chun, John K. Kim, Xiang-Dong Fu, and Yishi Jin*. Context-dependent modulation of Pol II CTD phosphatase SSUP-72 regulates alternative polyadenylation in neuronal development. Genes & Development, 29(22):2377–2390, November 2015.
Alternative polyadenylation (APA) is widespread in neuronal development and activity-mediated neural plasticity. However, the underlying molecular mechanisms are largely unknown. We used systematic genetic studies and genome-wide surveys of the transcriptional landscape to identify a context-dependent regulatory pathway controlling APA in the Caenorhabdit...
Yukiko Komeno#, Yi-Jou Huang#, Jinsong Qiu, Leo Lin, YiJun Xu, Yu Zhou, Liang Chen, Dora D. Monterroza, Hairi Li, Russell C. DeKelver, Ming Yan, Xiang-Dong Fu*, and Dong-Er Zhang*. SRSF2 Is Essential for Hematopoiesis, and Its Myelodysplastic Syndrome-Related Mutations Dysregulate Alternative Pre-mRNA Splicing. Molecular and Cellular Biology, 35(17):3071–3082, September 2015.
Myelodysplastic syndromes (MDS) are a group of neoplasms that are ineffective in generating multiple lineages of myeloid cells and have various risks to progress to acute myeloid leukemia. Recent genome-wide sequencing studies reveal that mutations in genes of splicing factors are commonly associated with MDS. However, the importance of these splicing fac...
Zhiqiang Cai, Ran Cao, Kai Zhang, Yuanchao Xue, Chen Zhang, Yu Zhou, Jie Zhou, Hui Sun, and Xiang-Dong Fu*. Oncogenic miR-17/20a Forms a Positive Feed-forward Loop with the p53 Kinase DAPK3 to Promote Tumorigenesis. Journal of Biological Chemistry, 290(32):19967–19975, August 2015.
MicroRNAs (miRs) are a class of small regulatory RNAs that have been implicated in diverse biological pathways, including cancer. miR-17/20a encoded by the c13orf25 locus is among the first miRs discovered to have oncogenic functions. The E2F family members have been established as the targets for these oncomiRs, which form a negative feedback loop to con...
Chaoliang Wei, Jinsong Qiu, Yu Zhou, Yuanchao Xue, Jing Hu, Kunfu Ouyang, Indroneal Banerjee, Caimei Zhang, Biyi Chen, Hairi Li, Ju Chen, Long-Sheng Song, and Xiang-Dong Fu*. Repression of the Central Splicing Regulator RBFox2 Is Functionally Linked to Pressure Overload-Induced Heart Failure. Cell Reports, 10(9):1521–1533, March 2015.
Heart failure is characterized by the transition from an initial compensatory response to decompensation, which can be partially mimicked by transverse aortic constriction (TAC) in rodent models. Numerous signaling molecules have been shown to be part of the compensatory program, but relatively little is known about the transition to decompensation that l...
Shuying Sun#, Shuo-Chien Ling#, Jinsong Qiu, Claudio P. Albuquerque, Yu Zhou, Seiya Tokunaga, Hairi Li, Haiyan Qiu, Anh Bui, Gene W. Yeo, Eric J. Huang, Kevin Eggan, Huilin Zhou, Xiang-Dong Fu, Clotilde Lagier-Tourenne, and Don W. Cleveland*. ALS-causative mutations in FUS/TLS confer gain and loss of function by altered association with SMN and U1-snRNP. Nature Communications, 6:6171, December 2015.
The RNA-binding protein FUS/TLS, mutation in which is causative of the fatal motor neuron disease amyotrophic lateral sclerosis (ALS), is demonstrated to directly bind to the U1-snRNP and SMN complexes. ALS-causative mutations in FUS/TLS are shown to abnormally enhance their interaction with SMN and dysregulate its function, including loss of Gems and alt...
Nova Fong#, Hyunmin Kim#, Yu Zhou, Xiong Ji, Jinsong Qiu, Tassa Saldi, Katrina Diener, Ken Jones, Xiang-Dong Fu, and David L. Bentley*. Pre-mRNA splicing is facilitated by an optimal RNA polymerase II elongation rate. Genes & Development, 28(23):2663–2676, December 2014.
Alternative splicing modulates expression of most human genes. The kinetic model of cotranscriptional splicing suggests that slow elongation expands and that fast elongation compresses the ‘‘window of opportunity’’ for recognition of upstream splice sites, thereby increasing or decreasing inclusion of alternative exons. We tested the model using RNA polym...
Changwei Shao#, Bo Yang#, Tongbin Wu#, Jie Huang, Peng Tang, Yu Zhou, Jie Zhou, Jinsong Qiu, Li Jiang, Hairi Li, Geng Chen, Hui Sun, Yi Zhang, Alain Denise, Dong-Er Zhang, and Xiang-Dong Fu*. Mechanisms for U2AF to define 3′ splice sites and regulate alternative splicing in the human genome. Nature Structural & Molecular Biology, 21(11):997–1005, November 2014.
The U2AF heterodimer has been well studied for its role in defining functional 3â €2 splice sites in pre-mRNA splicing, but many fundamental questions still remain unaddressed regarding the function of U2AF in mammalian genomes. Through genome-wide analysis of U2AF-RNA interactions, we report that U2AF has the capacity to directly define ∼88% of functiona...
Xiaorong Zhang, Xinxin Zuo, Bo Yang, Zongran Li, Yuanchao Xue, Yu Zhou, Jie Huang, Xiaolu Zhao, Jie Zhou, Yun Yan, Huiqiong Zhang, Peipei Guo, Hui Sun, Lin Guo, Yi Zhang, and Xiang-Dong Fu*. MicroRNA Directly Enhances Mitochondrial Translation during Muscle Differentiation. Cell, 158(3):607–619, July 2014.
MicroRNAs are well known to mediate translational repression and mRNA degradation in the cytoplasm. Various microRNAs have also been detected in membrane-compartmentalized organelles, but the functional significance has remained elusive. Here, we report that miR-1, a microRNA specifically induced during myogenesis, efficiently enters the mitochondria wher...
Lan-Tao Gou#, Peng Dai#, Jian-Hua Yang#, Yuanchao Xue, Yun-Ping Hu, Yu Zhou, Jun-Yan Kang, Xin Wang, Hairi Li, Min-Min Hua, Shuang Zhao, Si-Da Hu, Li-Gang Wu, Hui-Juan Shi, Yong Li, Xiang-Dong Fu, Liang-Hu Qu, En-Duo Wang, and Mo-Fang Liu*. Pachytene piRNAs instruct massive mRNA elimination during late spermiogenesis. Cell Research, 24(6):680–700, June 2014.
Spermatogenesis in mammals is characterized by two waves of piRNA expression: one corresponds to classic piRNAs responsible for silencing retrotransponsons and the second wave is predominantly derived from nontransposon intergenic regions in pachytene spermatocytes, but the function of these pachytene piRNAs is largely unknown. Here, we report the involve...
Pingping Wang, Zhihong Zhou, Anchang Hu, Claudio Ponte de Albuquerque, Yu Zhou, Lixin Hong, Emma Sierecki, Masahiko Ajiro, Michael Kruhlak, Curtis Harris, Kun-Liang Guan, Zhi-Ming Zheng, Alexandra C. Newton, Peiqing Sun, Huilin Zhou, and Xiang-Dong Fu*. Both Decreased and Increased SRPK1 Levels Promote Cancer by Interfering with PHLPP-Mediated Dephosphorylation of Akt. Molecular Cell, 54(3):378–391, May 2014.
Akt activation is a hallmark of human cancers. Here, we report a critical mechanism for regulation of Akt activity by the splicing kinase SRPK1, a downstream Akt target for transducing growth signals to regulate splicing. Surprisingly, we find that SRPK1 has a tumor suppressor function because ablation of SRPK1 in mouse embryonic fibroblasts induces cell ...
Areum Han, Peter Stoilov, Anthony J. Linares, Yu Zhou, Xiang-Dong Fu, and Douglas L. Black*. De Novo Prediction of PTBP1 Binding and Splicing Targets Reveals Unexpected Features of Its RNA Recognition and Function. PLoS Computational Biology, 10(1):e1003442, January 2014.
The splicing regulator Polypyrimidine Tract Binding Protein (PTBP1) has four RNA binding domains that each binds a short pyrimidine element, allowing recognition of diverse pyrimidine-rich sequences. This variation makes it difficult to evaluate PTBP1 binding to particular sites based on sequence alone and thus to identify target RNAs. Conversely, transcr...
Xiong Ji, Yu Zhou, Shatakshi Pandit, Jie Huang, Hairi Li, Charles Y. Lin, Rui Xiao, Christopher B. Burge, and Xiang-Dong Fu*. SR Proteins Collaborate with 7SK and Promoter-Associated Nascent RNA to Release Paused Polymerase. Cell, 153(4):855–868, May 2013.
RNAP II is frequently paused near gene promoters in mammals, and its transition to productive elongation requires active recruitment of P-TEFb, a cyclin-dependent kinase for RNAP II and other key transcription elongation factors. A fraction of P-TEFb is sequestered in an inhibitory complex containing the 7SK noncoding RNA, but it has been unclear how P-TE...
Yuanchao Xue, Kunfu Ouyang, Jie Huang, Yu Zhou, Hong Ouyang, Hairi Li, Gang Wang, Qijia Wu, Chaoliang Wei, Yanzhen Bi, Li Jiang, Zhiqiang Cai, Hui Sun, Kang Zhang, Yi Zhang, Ju Chen, and Xiang-Dong Fu*. Direct Conversion of Fibroblasts to Neurons by Reprogramming PTB-Regulated MicroRNA Circuits. Cell, 152(1-2):82–96, January 2013.
The induction of pluripotency or trans-differentiation of one cell type to another can be accomplished with cell-lineage-specific transcription factors. Here, we report that repression of a single RNA binding polypyrimidine-tract- binding (PTB) protein, which occurs during normal brain development via the action of miR-124, is sufficient to induce trans-d...
Zhihong Zhou, Jinsong Qiu, Wen Liu, Yu Zhou, Ryan M. Plocinik, Hairi Li, Qidong Hu, Gourisanker Ghosh, Joseph A. Adams, Michael G. Rosenfeld, and Xiang-Dong Fu*. The Akt-SRPK-SR Axis Constitutes a Major Pathway in Transducing EGF Signaling to Regulate Alternative Splicing in the Nucleus. Molecular Cell, 47(3):422–433, August 2012.
Pre-mRNA splicing is regulated by developmental and environmental cues, but little is known about how specific signals are transduced in mammalian cells to regulate this critical gene expression step. Here, we report massive reprogramming of alternative splicing in response to EGF signaling. By blocking individual branches in EGF signaling, we found that ...
Hairi Li, Hongyan Zhou, Dong Wang, Jinsong Qiu, Yu Zhou, Xiangqiang Li, Michael G. Rosenfeld*, Sheng Ding*, and Xiang-Dong Fu*. Versatile pathway-centric approach based on high-throughput sequencing to anticancer drug discovery. Proceedings of the National Academy of Sciences, 109(12):4609–4614, March 2012.
The advent of powerful genomics technologies has uncovered many fundamental aspects of biology, including the mechanisms of cancer; however, it has not been appropriately matched by the development of global approaches to discover new medicines against human diseases. Here we describe a unique high-throughput screening strategy by high-throughput sequenci...
Rui Xiao#, Peng Tang#, Bo Yang, Jie Huang, Yu Zhou, Changwei Shao, Hairi Li, Hui Sun, Yi Zhang*, and Xiang-Dong Fu*. Nuclear Matrix Factor hnRNP U/SAF-A Exerts a Global Control of Alternative Splicing by Regulating U2 snRNP Maturation. Molecular Cell, 45(5):656–668, March 2012.
The nuclear matrix-associated hnRNP U/SAF-A protein has been implicated in diverse pathways from transcriptional regulation to telomere length control to X inactivation, but the precise mechanism underlying each of these processes has remained elusive. Here, we report hnRNP U as a regulator of SMN2 splicing from a custom RNAi screen. Genome-wide analysis ...
Kristi Fox-Walsh, Jeremy Davis-Turak, Yu Zhou, Hairi Li, and Xiang-Dong Fu*. A multiplex RNA-seq strategy to profile poly(A+) RNA: application to analysis of transcription response and 3' end formation. Genomics, 98(4):266–271, October 2011.
RNA-seq technologies are now replacing microarrays for profiling gene expression. Here we describe a robust RNA-seq strategy for multiplex analysis of RNA samples based on deep sequencing. First, an oligo-dT linked to an adaptor sequence is used to prime cDNA synthesis. Upon solid phase selection, second strand synthesis is initiated using a random primer...
Wei Liu, Yu Zhou, Zexi Hu, Tao Sun, Alain Denise, Xiang-Dong Fu*, and Yi Zhang*. Regulation of splicing enhancer activities by RNA secondary structures. FEBS Letters, 584(21):4401–4407, November 2010.
In this report, we studied the effect of RNA structures on the activity of exonic splicing enhancers on the SMN1 minigene model by engineering known ESEs into different positions of stable hairpins. We found that as short as 7-bp stem is sufficient to abolish the enhancer activity. When placing ESEs in the loop region, AG-rich ESEs are fully active, but a...
Fu Wang, Xiang-Dong Fu, Yu Zhou, and Yi Zhang*. Down-regulation of the cyclin E1 oncogene expression by microRNA-16-1 induces cell cycle arrest in human cancer cells. BMB reports, 42(11):725–730, November 2009.
Cyclin E1 (CCNE1), a positive regulator of the cell cycle, controls the transition of cells from G1 to S phase. In numerous human tumors, however, CCNE1 expression is frequently dysregulated, while the mechanism leading to its dysregulation remains incompletely defined. Herein, we showed that CCNE1 expression was subject to post-transcriptional regulation...
Wen-ping Tong, Yu Zhou, Xinxin Wang, Fan Yang, Kai-Lang Wu, Jianguo Wu, and Yi Zhang*. An accurate quantitative method for screening effective siRNA probes targeting a Hepatitis B virus transcript in single living cells. Biochemical and Biophysical Research Communications, 367(4):866–873, March 2008.
A dual fluorescence reporter plasmid expressing EGFP and DsRed-Monomer from separate promoters was constructed for quantitative flow cytometry analysis. Cloning the hepatitis B virus (HBV) X gene into the 3′ UTR region of DsRed-Monomer allowed quantifying the efficacy of ten siRNAs designed according to the accessibility of HBx mRNA measured in vitro. Usi...
Olivier Namy, Yu Zhou, Sarath Gundllapalli, Carla R. Polycarpo, Alain Denise, Jean-Pierre Rousset, Dieter Söll, and Alexandre Ambrogelly*. Adding pyrrolysine to the Escherichia coli genetic code. FEBS letters, 581(27):5282–5288, November 2007.
Pyrrolysyl-tRNA synthetase and its cognate suppressor tRNAPyl mediate pyrrolysine (Pyl) insertion at in frame UAG codons. The presence of an RNA hairpin structure named Pyl insertion structure (PYLIS) downstream of the suppression site has been shown to stimulate the insertion of Pyl in archaea. We study here the impact of the presence of PYLIS on the lev...
Tai-Yuan Li#, Ping Yin#, Yu Zhou, Yi Zhang*, Yong-Ying Zhang, and Tseh-an Chen. Characterization of the replicon of a 51-kb native plasmid from the gram-positive bacterium Leifsonia xyli subsp. cynodontis. FEMS microbiology letters, 236(1):33–39, July 2004.
The 4992-bp replicon of a large cryptic plasmid in the gram-positive bacterium Leifsonia xyli subsp. cynodontis was identified and sequenced. The replicon encoded two proteins essential for plasmid replication and stability. The putative replication protein (RepA) is homologous to that of the plasmids in mycobacterial pLR7 family, while the putative ParA ...