HNRNPA2B1 Is a Mediator of m6A-Dependent Nuclear RNA Processing Events
Open accessAbstract
N(6)-methyladenosine (m(6)A) is the most abundant internal modification of messenger RNA. While the presence of m(6)A on transcripts can impact nuclear RNA fates, a reader of this mark that mediates processing of nuclear transcripts has not been identified. We find that the RNA-binding protein HNRNPA2B1 binds m(6)A-bearing RNAs in vivo and in vitro and its biochemical footprint matches the m(6)A consensus motif. HNRNPA2B1 directly binds a set of nuclear transcripts and elicits similar alternative splicing effects as the m(6)A writer METTL3. Moreover, HNRNPA2B1 binds to m(6)A marks in a subset of primary miRNA transcripts, interacts with the microRNA Microprocessor complex protein DGCR8, and promotes primary miRNA processing. Also, HNRNPA2B1 loss and METTL3 depletion cause similar processing defects for these pri-miRNA precursors. We propose HNRNPA2B1 to be a nuclear reader of the m(6)A mark and to mediate, in part, this mark's effects on primary microRNA processing and alternative splicing. PAPERCLIP.
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HNRNPA2B1 and HNRNPC exhibit selective binding to mRNAs containing m6A.
“According to a previous study, the HNRNP proteins HNRNPA2B1 and HNRNPC exhibit selective binding to mRNAs containing m6A.364,365”
From Epigenetic regulation in major depression and other stress-related disorders: molecular mechanisms, clinical relevance and therapeutic potential (2023) · cites this paper as [364]
The Results section ('HNRNPA2B1 binds methylated RNA'; page unavailable) reports that HNRNPA2B1 preferentially binds m6A-containing RNA. The Results section on transcriptome binding says hnRNPC binds near, rather than directly to, the m6A consensus motif; it does not establish selective binding to m6A-containing mRNAs for hnRNPC. (LLM, conf=0.86)
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“According to a previous study, the HNRNP proteins HNRNPA2B1 and HNRNPC exhibit selective binding to mRNAs containing m(6)A.(364,365) HNRNPA2B1 may be one of eight genes associated with postpartum depression and may have diagnostic value.”
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- Authors
- Alarcón, C. R., Goodarzi, H., Lee, H., Liu, X., Tavazoie, S., & Tavazoie, S. F.
- Affiliations
- Rockefeller University (US)
- Columbia University (US)
- Corresponding author
- Tavazoie, Sohail F.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2015-09
- Volume
- 162
- Issue
- 6
- Pages
- 1299-1308
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC4673968
- OpenAlex
- W1895681508
- Cited by
- 1,514
- References
- 4
- Citations by year
- 2026: 108 · 2025: 143 · 2024: 183 · 2023: 225 · 2022: 215 · 2021: 206 · 2020: 155 · 2019: 93 · 2018: 79 · 2017: 64 · 2016: 38 · 2015: 3 · 2014: 1
- FWCI
- 26.65
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- U.S. Department of Defense
- National Institutes of Health
- National Human Genome Research Institute (R01HG003219)
- National Cancer Institute (R00CA194077, K99CA194077, T32CA009673)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA modifications and cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA regulation and disease
- Keywords
- HNRNPA2B1, N6-methyladenosine, m6A reader, nuclear RNA processing, alternative splicing, METTL3, DGCR8, microprocessor complex, RNA-binding proteins, mRNA modification
- MeSH terms
- Adenosine, Cell Nucleus, HeLa Cells, Humans, Methylation, RNA, RNA Processing, Post-Transcriptional, RNA-Binding Proteins, Alternative Splicing, Heterogeneous-Nuclear Ribonucleoprotein Group A-B, Cell Line, Tumor, HEK293 Cells, Transcriptome
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