Molecular basis for the specific and multivariant recognitions of RNA substrates by human hnRNP A2/B1.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 29379020.
- Also identified by DOI 10.1038/s41467-017-02770-z and PMC identifier 5789076.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
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 m<sup>6</sup>A "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 m<sup>6</sup>A through a "m<sup>6</sup>A switch" mechanism, instead of acting as a direct "reader" of m<sup>6</sup>A modification.
Medical subject headings
- Heterogeneous-Nuclear Ribonucleoprotein Group A-B
- RNA Recognition Motif