N6-methyladenosine alters RNA structure to regulate binding of a low-complexity protein.

TitreN6-methyladenosine alters RNA structure to regulate binding of a low-complexity protein.
Publication TypeJournal Article
Year of Publication2017
AuthorsLiu N, Zhou KI, Parisien M, Dai Q, Diatchenko L, Pan T
JournalNucleic Acids Res
Date Published2017 Feb 25
ISSN1362-4962
Abstract

N6-methyladenosine (m6A) is the most abundant internal modification in eukaryotic messenger RNA (mRNA), and affects almost every stage of the mRNA life cycle. The YTH-domain proteins can specifically recognize m6A modification to control mRNA maturation, translation and decay. m6A can also alter RNA structures to affect RNA-protein interactions in cells. Here, we show that m6A increases the accessibility of its surrounding RNA sequence to bind heterogeneous nuclear ribonucleoprotein G (HNRNPG). Furthermore, HNRNPG binds m6A-methylated RNAs through its C-terminal low-complexity region, which self-assembles into large particles in vitro. The Arg-Gly-Gly repeats within the low-complexity region are required for binding to the RNA motif exposed by m6A methylation. We identified 13,191 m6A sites in the transcriptome that regulate RNA-HNRNPG interaction and thereby alter the expression and alternative splicing pattern of target mRNAs. Low-complexity regions are pervasive among mRNA binding proteins. Our results show that m6A-dependent RNA structural alterations can promote direct binding of m6A-modified RNAs to low-complexity regions in RNA binding proteins.

DOI10.1093/nar/gkx141
Alternate JournalNucleic Acids Res.
PubMed ID28334903
Grant ListF30 GM120917 / GM / NIGMS NIH HHS / United States
T32 GM007281 / GM / NIGMS NIH HHS / United States