HNRNPA2B1 is a mediator of m6A-dependent nuclear RNA processing events

By Claudio R. Alarcón, H. Goodarzi, Hyeseung Lee, Xuhang Liu, Saeed Tavazoie, S. Tavazoie. Cell, 2015

1,358 citations recorded by the source corpus.

SUMMARY N6-methyladenosine (m6A) is the most abundant internal modification of messenger RNA. While the presence of m6A on transcripts can impact alternative splicing, a nuclear reader of this mark that mediates the processing of nuclear transcripts has not been identified. We find that the RNA-binding HNRNPA2B1 protein binds m6A-bearing RNAs in vivo and in vitro and its biochemical footprint matches the m6A consensus motif. HNRNPA2B1 directly binds a set of nuclear transcripts and modulates their alternative splicing in a similar manner as the m6A ‘writer’ METTL3. Moreover, HNRNPA2B1 binds to m6A marks in a subset of primary-miRNA transcripts, interacts with the microRNA Microprocessor complex protein DGCR8, and promotes primary miRNA processing—phenocopying the effect of METTL3 depletion on the processing of these precursor transcripts. We propose HNRNPA2B1 to be a nuclear reader of the m6A mark and to mediate, in part, this mark’s effects on primary microRNA processing and alternative splicing.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/6260eb60dd26c01aa607b2b340d188ecd40f9b34

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Citations in the corpus

Rethinking m6A Readers, Writers, and Erasers (2017, background): “This protein was originally identified as a nuclear m6A-binding protein that affects microRNA biogenesis (Alarcon et al. 2015a,b).”
YTHDC1 mediates nuclear export of N6-methyladenosine methylated mRNAs (2017, background): “However, the alternative splicing events observed following knockdown of YTHDC1 show only weak negative correlations to those observed following knockdown of METTL3 (Figure 4—figure supplement 2B) (Alarcón et al., 2015).”
The potential role of RNA N6-methyladenosine in Cancer progression (2020, positive): “HNRNPA2/B1 can recognize m6A on a subset of primary microRNA (primiRNA) transcripts and interact with drosha ribonuclease III (DROSHA) and DiGeorge syndrome critical region 8 (DGCR8), thus facilitating pri-miRNA processing [37].”
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).”
METTL14 suppresses the metastatic potential of hepatocellular carcinoma by modulating N6‐methyladenosine‐dependent primary MicroRNA processing (2017, background): “In addition, some miRNAs contain m(6)A tags in their pri-miRNA and are involved in DGCR8-dependent pri-miRNA processing.((23,24)) We then measured the miRNAs and their pri-miRNAs in METTL14-depleted cells and found that miR126 was significantly decreased in METTL14-depleted cells (Supporting Fig.”
METTL3 promotes translation in human cancer cells (2016, methodology): “Q5 SiteDirected Mutagenesis Kit (NEB) was used to generate the METTL3 catalytic mutant (aa395-398, DPPW / APPA) (Alarcón et al., 2015b).”