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Title:
Molecular basis for the specific and multivariant recognitions of RNA substrates by human hnRNP A2/B1 | Nature Communications
Description:
Human hnRNP A2/B1 is an RNA-binding protein that plays important roles in many biological processes, including maturation, transport, and metabolism of mRNA, and gene regulation of long noncoding RNAs. hnRNP A2/B1 was reported to control the microRNAs sorting to exosomes and promote primary microRNA processing as a potential m6A “reader.” hnRNP A2/B1 contains two RNA recognition motifs that provide sequence-specific recognition of RNA substrates. Here, we determine crystal structures of tandem RRM domains of hnRNP A2/B1 in complex with various RNA substrates, elucidating specific recognitions of AGG and UAG motifs by RRM1 and RRM2 domains, respectively. Further structural and biochemical results demonstrate multivariant binding modes for sequence-diversified RNA substrates, supporting a RNA matchmaker mechanism in hnRNP A2/B1 function. Moreover, our studies in combination with bioinformatic analysis suggest that hnRNP A2/B1 may mediate effects of m6A through a “m6A switch” mechanism, instead of acting as a direct “reader” of m6A modification. RNA-binding protein hnRNP A2/B1 is suggested to promote miRNA processing as a m6A
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Keywords {🔍}
rna, hnrnp, rrm, pubmed, fig, binding, article, mer, complex, google, scholar, cas, structure, recognition, data, rrms, central, motif, nuclear, nature, supplementary, analysis, protein, sites, interactions, specific, colored, proteins, hydrogen, structures, itc, rnabinding, chain, side, ythdc, crystal, study, domains, rnas, molecule, bind, determined, recognized, substrates, results, modification, domain, bound, cell, biol,
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nature portfolio privacy policy model-building tools n-terminal hexahistidine-sumo fusions advertising full-length hnrnp a2/b1 medical research 2 mm isopropyl-β-d-thiogalactoside m6a individual-nucleotide-resolution crosslinking social media hnrnp a2/b1-binding sites c-terminal glycine-rich region recent clip-seq data reprints hnrnp a2/b1-10-nt complex human hnrnp a2/b1 hnrnp a2/b1 recognizes nature 495 nature 499 nature 475 nature 537 nature 518 nature 519 nature sequence-specific rna-binding properties heterogeneous nuclear ribonucleoproteins hampton research research progress hnrnp a2/b1 carrying hnrnp a2/b1 binds pyrimidine-rich uu sequence arginine/glycine-rich box3 hnrnp a2/b1 targets n6-methylated adenosine modification hnrnp a2/b1 associates hnrnp a2/b1 mediating hnrnp a2/b1 recognizing hnrnp a2/b1 comprises hnrnp a2/b1 prefers hnrnp a2/b1 offers hnrnp a2/b1 constructs nuclear m6a-seq data au-rich element rna unlike hnrnp a2/b1 hnrnp a2b1–rna complex structure hnrnp a2/b1-8-nt hnrnp a2/b1 interact hnrnp a2/b1 proteins hnrnp a2/b1 molecules arginine-glycine-glycine box
Questions {❓}
- Sequence-specific binding of single-stranded RNA: is there a code for recognition?
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headline:Molecular basis for the specific and multivariant recognitions of RNA substrates by human hnRNP A2/B1
description:Human hnRNP A2/B1 is an RNA-binding protein that plays important roles in many biological processes, including maturation, transport, and metabolism of mRNA, and gene regulation of long noncoding RNAs. hnRNP A2/B1 was reported to control the microRNAs sorting to exosomes and promote primary microRNA processing as a potential m6A âreader.â hnRNP A2/B1 contains two RNA recognition motifs that provide sequence-specific recognition of RNA substrates. Here, we determine crystal structures of tandem RRM domains of hnRNP A2/B1 in complex with various RNA substrates, elucidating specific recognitions of AGG and UAG motifs by RRM1 and RRM2 domains, respectively. Further structural and biochemical results demonstrate multivariant binding modes for sequence-diversified RNA substrates, supporting a RNA matchmaker mechanism in hnRNP A2/B1 function. Moreover, our studies in combination with bioinformatic analysis suggest that hnRNP A2/B1 may mediate effects of m6A through a âm6A switchâ mechanism, instead of acting as a direct âreaderâ of m6A modification. RNA-binding protein hnRNP A2/B1 is suggested to promote miRNA processing as a m6A 'reader'. Here, the authors determine crystal structures of RRM domains of hnRNP A2/B1 in complex with various RNA substrates and determine that hnRNP A2/B1 may function as an auxiliary factor in 'm6A switch' instead.
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description:Human hnRNP A2/B1 is an RNA-binding protein that plays important roles in many biological processes, including maturation, transport, and metabolism of mRNA, and gene regulation of long noncoding RNAs. hnRNP A2/B1 was reported to control the microRNAs sorting to exosomes and promote primary microRNA processing as a potential m6A âreader.â hnRNP A2/B1 contains two RNA recognition motifs that provide sequence-specific recognition of RNA substrates. Here, we determine crystal structures of tandem RRM domains of hnRNP A2/B1 in complex with various RNA substrates, elucidating specific recognitions of AGG and UAG motifs by RRM1 and RRM2 domains, respectively. Further structural and biochemical results demonstrate multivariant binding modes for sequence-diversified RNA substrates, supporting a RNA matchmaker mechanism in hnRNP A2/B1 function. Moreover, our studies in combination with bioinformatic analysis suggest that hnRNP A2/B1 may mediate effects of m6A through a âm6A switchâ mechanism, instead of acting as a direct âreaderâ of m6A modification. RNA-binding protein hnRNP A2/B1 is suggested to promote miRNA processing as a m6A 'reader'. Here, the authors determine crystal structures of RRM domains of hnRNP A2/B1 in complex with various RNA substrates and determine that hnRNP A2/B1 may function as an auxiliary factor in 'm6A switch' instead.
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