HnRNP L and HnRNP A1 Induce Extended U1 SnRNA Interactions with an Exon to Repress Spliceosome Assembly

Overview

Journal Mol Cell

Publisher Cell Press

Specialty Cell Biology

Date 2013 Feb 12

PMID 23394998

Citations 47

Authors

Ni-Ting Chiou

Ganesh Shankarling

Kristen W Lynch

Affiliations

Soon will be listed here.

Abstract

Pre-mRNA splicing is catalyzed through the activity of the spliceosome, a dynamic enzymatic complex. Forcing aberrant interactions within the spliceosome can reduce splicing efficiency and alter splice site choice; however, it is unknown whether such alterations are naturally exploited mechanisms of splicing regulation. Here, we demonstrate that hnRNP L represses CD45 exon 4 by recruiting hnRNP A1 to a sequence upstream of the 5' splice site. Together, hnRNP L and A1 induce extended contacts between the 5' splice site-bound U1 snRNA and neighboring exonic sequences that, in turn, inhibit stable association of U6 snRNA and subsequent catalysis. Importantly, analysis of several exons regulated by hnRNP L shows a clear relationship between the potential for binding of hnRNP A1 and U1 snRNA and the effect of hnRNP L on splicing. Together, our results demonstrate that conformational perturbations within the spliceosome are a naturally occurring and generalizable mechanism for controlling alternative splicing decisions.

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