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Liu, Bei; Merriman, Dawn K.; Choi, Seung H.; Schumacher, Maria A.; Plangger, Raphael; Kreutz, Christoph; Horner, Stacy M.; Meyer, Kate D.; Al-Hashimi, Hashim M.
Nature communications, 07/2018, Letnik: 9, Številka: 1Journal Article
Abstract N 6 -Methyladenosine (m 6 A) is an abundant post-transcriptional RNA modification that influences multiple aspects of gene expression. In addition to recruiting proteins, m 6 A can modulate RNA function by destabilizing base pairing. Here, we show that when neighbored by a 5ʹ bulge, m 6 A stabilizes m 6 A–U base pairs, and global RNA structure by ~1 kcal mol −1 . The bulge most likely provides the flexibility needed to allow optimal stacking between the methyl group and 3ʹ neighbor through a conformation that is stabilized by Mg 2+ . A bias toward this motif can help explain the global impact of methylation on RNA structure in transcriptome-wide studies. While m 6 A embedded in duplex RNA is poorly recognized by the YTH domain reader protein and m 6 A antibodies, both readily recognize m 6 A in this newly identified motif. The results uncover potentially abundant and functional m 6 A motifs that can modulate the epitranscriptomic structure landscape with important implications for the interpretation of transcriptome-wide data.
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