PT  - JOURNAL ARTICLE
AU  - Baixing Wu
AU  - Shichen Su
AU  - Deepak P. Patil
AU  - Hehua Liu
AU  - Jianhua Gan
AU  - Samie R. Jaffrey
AU  - Jinbiao Ma
TI  - Molecular basis for the specific and multivariate recognitions of RNA substrates by human hnRNPA2/B1
AID  - 10.1101/144345
DP  - 2017 Jan 01
TA  - bioRxiv
PG  - 144345
4099  - http://biorxiv.org/content/early/2017/06/01/144345.short
4100  - http://biorxiv.org/content/early/2017/06/01/144345.full
AB  - Human hnRNPA2/B1 is an RNA-binding protein that plays important roles in a variety of biological processes, from mRNA maturation, trafficking and translation to regulation of gene expression mediated by long non-coding RNAs and microRNAs. hnRNPA2/B1 contains two RNA recognition motifs (RRM) that provide sequence-specific recognition of widespread RNA substrates including recently reported m6A-containing motifs. Here we determined the first crystal structures of tandem RRM domains of hnRNPA2/B1 in complex with various RNA substrates. Our structures reveal that hnRNPA2/B1 can bind two RNA elements in an antiparallel fashion with a sequence preference for AGG and UAG by RRM1 and RRM2, respectively, suggesting an RNA matchmaker mechanism during the hnRNPA2/B1 function. However, our combined studies did not observe specific binding of m6A by either the RRM domains or the full-length hnRNPA2/B1, implying that the “reader” function of hnRNPA2/B1 may adopt an unknown mechanism that remains to be characterized.