RT Journal Article
SR Electronic
T1 Molecular basis for the specific and multivariate recognitions of RNA substrates by human hnRNPA2/B1
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 144345
DO 10.1101/144345
A1 Baixing Wu
A1 Shichen Su
A1 Deepak P. Patil
A1 Hehua Liu
A1 Jianhua Gan
A1 Samie R. Jaffrey
A1 Jinbiao Ma
YR 2017
UL http://biorxiv.org/content/early/2017/06/01/144345.abstract
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.