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. 2016 Aug;13(8):692-8.
doi: 10.1038/nmeth.3898. Epub 2016 Jul 4.

m(6)A-LAIC-seq reveals the census and complexity of the m(6)A epitranscriptome

Benoit Molinie  1 , Jinkai Wang  2 , Kok Seong Lim  3 , Roman Hillebrand  3 , Zhi-Xiang Lu  2 , Nicholas Van Wittenberghe  1 , Benjamin D Howard  1 , Kaveh Daneshvar  1 , Alan C Mullen  1   4 , Peter Dedon  3 , Yi Xing  2 , Cosmas C Giallourakis  1   4   5
Affiliations

m(6)A-LAIC-seq reveals the census and complexity of the m(6)A epitranscriptome

Benoit Molinie et al. Nat Methods. 2016 Aug.

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.

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Conflict of interest statement

Competing financial interests

C.C.G., Y.X., B.M., and J.W. are in the process of filing a patent application for m6A-LAIC-seq.

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