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Nucleic Acids Res. 2017 Jun 2;45(10):6051-6063. doi: 10.1093/nar/gkx141.

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

Author information

1
Department of Chemistry, University of Chicago, Chicago, IL 60637, USA.
2
Medical Scientist Training Program, University of Chicago, Chicago, IL 60637, USA.
3
The Alan Edwards Centre for Research on Pain, Department of Dentistry, McGill University, Montréal, Québec H3A 0G1, Canada.
4
Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, IL 60637, USA.
5
Institute of Biophysical Dynamics, University of Chicago, Chicago, IL 60637, USA.

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.

PMID:
28334903
PMCID:
PMC5449601
DOI:
10.1093/nar/gkx141
[Indexed for MEDLINE]
Free PMC Article

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