title: HNRNPA2B1 Is a Mediator of m(6)A-Dependent Nuclear RNA Processing Events.
abstract: 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.
authors: Laboratory of Systems Cancer Biology, Rockefeller University, New York, NY 10065, USA.
authors: Claudio R
authors: CR
authors: Alarcón
authors: Laboratory of Systems Cancer Biology, Rockefeller University, New York, NY 10065, USA.
authors: Hani
authors: H
authors: Goodarzi
authors: Laboratory of Systems Cancer Biology, Rockefeller University, New York, NY 10065, USA.
authors: Hyeseung
authors: H
authors: Lee
authors: Laboratory of Systems Cancer Biology, Rockefeller University, New York, NY 10065, USA.
authors: Xuhang
authors: X
authors: Liu
authors: Department of Biochemistry and Molecular Biophysics and Department of Systems Biology, Columbia University, New York, NY 10032, USA.
authors: Saeed
authors: S
authors: Tavazoie
authors: Laboratory of Systems Cancer Biology, Rockefeller University, New York, NY 10065, USA. Electronic address: stavazoie@mail.rockefeller.edu.
authors: Sohail F
authors: SF
authors: Tavazoie
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives* / Q000378:metabolism; D017398:Alternative Splicing; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D057809:HEK293 Cells; D006367:HeLa Cells; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B / Q000378:metabolism*; D006801:Humans; D008745:Methylation; D012313:RNA / Q000378:metabolism; D012323:RNA Processing, Post-Transcriptional; D016601:RNA-Binding Proteins / Q000378:metabolism; D059467:Transcriptome
chemical_list: C474043:DGCR8 protein, human; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B; D016601:RNA-Binding Proteins; C439768:hnRNP A2; D012313:RNA; C010223:N-methyladenosine; D000241:Adenosine