报告题目: Elucidating the complexity of the mammalian m6A epitranscriptome
报 告 人: 邢毅 加利福尼亚大学洛杉矶分校教授
报告时间: 2016年12月20日(星期二) 11:00
报告地点: 中科院生物物理所图书馆二楼报告厅
主 持 人: 俞洋 研究员
报告人简介
Professor 2016-
Department of Microbiology, Immunology, and Molecular Genetics
University of California, Los Angeles, California, USA
Director 2014-October 21, 2016
Bioinformatics Interdepartmental Graduate Program
University of California, Los Angeles, California, USA
报告摘要
N6-methyladenosine (m6A) is a widespread reversible chemical modification of RNAs, implicated in many aspects of RNA metabolism. Little quantitative information exists as to how many transcript copies of particular genes are m6A modified (“m6A levels”), or the relationship of m6A modification(s) to alternative RNA isoforms. To deconvolute the m6A epitranscriptome, we developed m6A level and isoform-characterization sequencing (m6A-LAIC-seq). We found that cells exhibit a broad range of non-stoichiometric m6A levels with cell type specificity. At the level of isoform characterization, we discovered widespread differences in use of tandem alternative polyadenylation (APA) sites by methylated and nonmethylated transcript isoforms of individual genes. Strikingly, there is a strong bias for methylated transcripts to be coupled with proximal APA sites, resulting in shortened 3’ untranslated regions (3'-UTRs), while nonmethylated transcript isoforms tend to use distal APA sites. m6A-LAIC-seq yields a new perspective on transcriptome complexity and links APA usage to m6A modifications.
研究成果
1.Molinie B.*, Wang J.*, Lim KS., Hillebrand R., Lu ZX., Wittenberghe NV., Howard BD.,Daneshvar K., Mullen A., Dedon P., Xing Y.+, Giallourakis C.+ (2016) m6A level and isoform characterization sequencing (m6A-LAIC-seq) reveals the census and complexity of the m6A epitranscriptome. Nature Methods. 13(8):692-8. (+ joint corresponding authors).
News story by: Genome Web.
Highlighted by: Shi H. & He C. (2016) A glance at N6-methyladenosine in transcript isoforms. Nature Methods. 13:624–625.
2. Park JW.+, Chung S., Rouchka E., Tseng YT., Xing Y.+ (2016) rMAPS: RNA map analysis and plotting server for alternative exon regulation. Nucleic Acids Research. 44(W1):W333- 8. (+ joint corresponding authors).
3.Damianov A., Ying Y., Lin CH., Lee JA., Tran D., Vashisht AA., Bahrami-Samani E., Xing Y., Martin KC., Wohlschlegel JA., Black DL. (2016) Rbfox splicing regulators are recruited to pre-mRNA as part of a novel multi-protein complex, LASR. Cell. 165(3): 606-619. PMCID: PMC4841943
4. Cieply B.*, Park JW.*, Nakauka-Ddamba A., Bebee TW., Guo Y., Shang X., Lengner CJ., Xing Y.+, Carstens RP.+ (2016) Multiphasic and dynamic changes in alternative splicing during induction of pluripotency are coordinated by numerous RNA binding proteins. Cell Reports. 15(2):247-255. (+ joint corresponding authors).