Cooperative-binding and splicing-repressive properties of hnRNP A1

Okunola, H. L., Krainer, A. R. (October 2009) Cooperative-binding and splicing-repressive properties of hnRNP A1. Mol Cell Biol, 29 (20). pp. 5620-5631.

URL: http://www.ncbi.nlm.nih.gov/pubmed/19667073
DOI: 10.1128/MCB.01678-08

Abstract

hnRNP A1 binds to RNA in a cooperative manner. Initial hnRNP A1 binding to an exonic splicing silencer (ESS) at the 3' end of HIV-1 tat exon 3, which is a high-affinity site, is followed by cooperative spreading in a 3' to 5' direction. As hnRNP A1 propagates towards the 5' end of the exon, it antagonizes binding of a serine/arginine-rich (SR) protein to an exonic splicing enhancer (ESE), thereby inhibiting splicing at that exon's alternative 3' splice site. Tat exon 3 and the preceding intron of HIV-1 pre-mRNA can fold into an elaborate RNA secondary structure in solution, which could potentially influence hnRNP A1 binding. We report here that hnRNP A1 binding and splicing repression can occur on an unstructured RNA. Moreover, hnRNP A1 can effectively unwind an RNA hairpin upon binding, displacing a bound protein. We further show that hnRNP A1 can also spread in a 5' to 3' direction, although when initial binding takes place in the middle of an RNA, spreading preferentially proceeds in a 3' to 5' direction. Finally, when two distant high-affinity sites are present on the same RNA, they facilitate cooperative spreading of hnRNP A1 between the two sites.

Item Type: Paper
Subjects: bioinformatics
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
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > RNA splicing
CSHL Authors:
Communities: CSHL labs > Krainer lab
CSHL Cancer Center Shared Resources > Antibody and Phage Display Service
CSHL Cancer Center Shared Resources > DNA Sequencing Service
Depositing User: Matt Covey
Date: October 2009
Date Deposited: 21 Feb 2013 21:16
Last Modified: 30 Dec 2014 16:31
PMCID: PMC2756886
Related URLs:
URI: http://repository.cshl.edu/id/eprint/27350

Actions (login required)

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