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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Liu, N; Zhou, KI; Parisien, M; Dai, Q; Diatchenko, L; Pan, T

Published Date

  • June 2, 2017

Published In

Volume / Issue

  • 45 / 10

Start / End Page

  • 6051 - 6063

PubMed ID

  • 28334903

Pubmed Central ID

  • PMC5449601

Electronic International Standard Serial Number (EISSN)

  • 1362-4962

Digital Object Identifier (DOI)

  • 10.1093/nar/gkx141

Language

  • eng

Conference Location

  • England