A potentially abundant junctional RNA motif stabilized by m6A and Mg2+

Bei Liu, Dawn K. Merriman, Seung H. Choi, Maria A. Schumacher, Raphael Plangger, Christoph Kreutz, Stacy M. Horner, Kate D. Meyer and Hashim M. Al-Hashimi ()
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Bei Liu: Duke University School of Medicine
Dawn K. Merriman: Duke University
Seung H. Choi: Duke University School of Medicine
Maria A. Schumacher: Duke University School of Medicine
Raphael Plangger: University of Innsbruck
Christoph Kreutz: University of Innsbruck
Stacy M. Horner: Duke University School of Medicine
Kate D. Meyer: Duke University School of Medicine
Hashim M. Al-Hashimi: Duke University School of Medicine

Nature Communications, 2018, vol. 9, issue 1, 1-10

Abstract: Abstract N6-Methyladenosine (m6A) is an abundant post-transcriptional RNA modification that influences multiple aspects of gene expression. In addition to recruiting proteins, m6A can modulate RNA function by destabilizing base pairing. Here, we show that when neighbored by a 5ʹ bulge, m6A stabilizes m6A–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 Mg2+. A bias toward this motif can help explain the global impact of methylation on RNA structure in transcriptome-wide studies. While m6A embedded in duplex RNA is poorly recognized by the YTH domain reader protein and m6A antibodies, both readily recognize m6A in this newly identified motif. The results uncover potentially abundant and functional m6A motifs that can modulate the epitranscriptomic structure landscape with important implications for the interpretation of transcriptome-wide data.

Date: 2018
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DOI: 10.1038/s41467-018-05243-z

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