N 6-methyladenosine alters RNA structure to regulate binding of a low-complexity protein

By Nian Liu, K. I. Zhou, Marc-André Parisien, Qing Dai, Luda Diatchenko, T. Pan. Nucleic Acids Research, 2017

700 citations recorded by the source corpus.

Abstract N 6-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.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/d72021bdcef96134d489fc9344ee7117da13bfe9

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In Molecular Biology

1. Chuan He
2. Hailing Shi
3. Jiangbo W
4. Phillip J Hsu
5. Ying Yang
6. Yu-Sheng Chen
7. Yun-Gui Yang
8. Samie R. Jaffrey

Citations in the corpus

• Where, when and how: context-dependent functions of RNA methylation writers, readers, and erasers (2019, background): “Several heterogeneous nuclear ribonucleoproteins (HNRNPs) fall into this category, including HNRNPC, HNRNPG, and HNRNPA2B1, which regulate alternative splicing or processing of target transcripts (Alarcon et al., 2015a; Liu et al., 2015; Liu et al., 2017; Wu et al., 2018).”
• m6A RNA methylation: from mechanisms to therapeutic potential (2021, neutral): “The RNA-binding proteins (RBPs) HNRNPC and HNRNPG are indirect “structural-switch” readers, that can selectively bind at “structural switches”, sites at which m 6 A alters the accessibility of proximal RNA sequence to facilitate binding of RBPs (Liu et al , 2015, 2017; Zhou et al , 2019).”
• Functions of N6-methyladenosine and its role in cancer (2019, background): “In molecular mechanism, m6A participates in almost all steps of RNA metabolism including mRNA translation, degradation, splicing, export and folding [11, 12].”
• Dynamic transcriptomic m6A decoration: writers, erasers, readers and functions in RNA metabolism (2018, background): “They do not bind to m6A directly, but instead, m6A serves as a structural switch to alter the RNA structure, which renders transcripts more accessible for binding by HNRNPC and HNRNPG. Cytoplasmic m6A readers After being processed from precursor transcripts, mature mRNAs containing m6A are further r”