Function of conserved domains of hnRNP A1 and other hnRNP A/B proteins.

Mayeda, A., Munroe, S. H., Caceres, J. F., Krainer, A. R. (November 1994) Function of conserved domains of hnRNP A1 and other hnRNP A/B proteins. EMBO Journal, 13 (22). pp. 5483-5495. ISSN 0261-4189

URL: http://www.ncbi.nlm.nih.gov/pubmed/7957114

Abstract

hnRNP A1 is a pre-mRNA binding protein that antagonizes the alternative splicing activity of splicing factors SF2/ASF or SC35, causing activation of distal 5' splice sites. The structural requirements for hnRNP A1 function were determined by mutagenesis of recombinant human hnRNP A1. Two conserved Phe residues in the RNP-1 submotif of each of two RNA recognition motifs appear to be involved in specific RNA-protein interactions and are essential for modulating alternative splicing. These residues are not required for general pre-mRNA binding or RNA annealing activity. The C-terminal Gly-rich domain is necessary for alternative splicing activity, for stable RNA binding and for optimal RNA annealing activity. hnRNP A1(B), which is an alternatively spliced isoform of hnRNP A1 with a longer Gly-rich domain, binds more strongly to pre-mRNA but has only limited alternative splicing activity. In contrast, hnRNP A2 and B1, which have 68% amino acid identity with hnRNP A1, bind more weakly to pre-mRNA and have stronger splice site switching activities than hnRNP A1. We propose that specific combinations of antagonistic hnRNP A/B and SR proteins are involved in regulating alternative splicing of distinct subsets of cellular pre-mRNAs.

Item Type: Paper
Uncontrolled Keywords: alternative splicing hnrnp a1 hnrnp a or b group proteins rna-protein interactions rna rna annealing pre-messenger-rna heterogeneous nuclear ribonucleoprotein splice-site selection tract-binding-protein complementary-dna strands premessenger rna sr proteins annealing activity complex protein-a1 terminal domain
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification
bioinformatics > genomics and proteomics > genetics & nucleic acid processing
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > nuclear ribonucleoprotein
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > pre-mRNA
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > splice site
CSHL Authors:
Communities: CSHL labs > Krainer lab
Depositing User: Matt Covey
Date: November 1994
Date Deposited: 11 Dec 2013 14:42
Last Modified: 11 Dec 2013 14:42
PMCID: PMC395506
URI: http://repository.cshl.edu/id/eprint/28949

Actions (login required)

Administrator's edit/view item Administrator's edit/view item
CSHL HomeAbout CSHLResearchEducationNews & FeaturesCampus & Public EventsCareersGiving