| Literature DB >> 27376769 |
Benoit Molinie1, Jinkai Wang2, Kok Seong Lim3, Roman Hillebrand3, Zhi-Xiang Lu2, Nicholas Van Wittenberghe1, Benjamin D Howard1, Kaveh Daneshvar1, Alan C Mullen1,4, Peter Dedon3, Yi Xing2, Cosmas C Giallourakis1,4,5.
Abstract
N(6)-Methyladenosine (m(6)A) is a widespread, reversible chemical modification of RNA molecules, implicated in many aspects of RNA metabolism. Little quantitative information exists as to either how many transcript copies of particular genes are m(6)A modified ('m(6)A levels') or the relationship of m(6)A modification(s) to alternative RNA isoforms. To deconvolute the m(6)A epitranscriptome, we developed m(6)A-level and isoform-characterization sequencing (m(6)A-LAIC-seq). We found that cells exhibit a broad range of nonstoichiometric m(6)A levels with cell-type specificity. At the level of isoform characterization, we discovered widespread differences in the 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, while nonmethylated transcript isoforms tend to use distal APA sites. m(6)A-LAIC-seq yields a new perspective on transcriptome complexity and links APA usage to m(6)A modifications.Entities:
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Year: 2016 PMID： 27376769 PMCID： PMC5704921 DOI： 10.1038/nmeth.3898
Source DB: PubMed Journal: Nat Methods ISSN： 1548-7091 Impact factor: 28.547