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HnRNP L represses exon splicing via a regulated exonic splicing silencer
Author(s) -
Rothrock Caryn R,
House Amy E,
Lynch Kristen W
Publication year - 2005
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/sj.emboj.7600745
Subject(s) - exon , rna splicing , heterogeneous nuclear ribonucleoprotein , heterogeneous ribonucleoprotein particle , gene silencing , biology , exonic splicing enhancer , alternative splicing , rna binding protein , ribonucleoprotein , microbiology and biotechnology , exon skipping , splice site mutation , genetics , gene , messenger rna , rna
Skipping of mammalian exons during pre‐mRNA splicing is commonly mediated by the activity of exonic splicing silencers (ESSs). We have recently identified a regulated ESS within variable exon 4 of the CD45 gene, named ESS1, that is necessary and sufficient for partial exon repression in resting T cells and has additional silencing activity upon T‐cell activation. In this study, we identify three heterogeneous nuclear ribonucleoproteins (hnRNPs) that bind specifically to ESS1. The binding of one of these proteins, hnRNP‐L, is significantly decreased by mutations that disrupt both the basal and induced activities of ESS1. Recombinant hnRNP‐L functions to repress exon inclusion in vitro in an ESS1‐dependent manner. Moreover, depletion of hnRNP‐L, either in vitro or in vivo , leads to increased exon inclusion. In contrast, the other ESS1‐binding proteins, PTB and hnRNP E2, do not discriminate between wild‐type and mutant ESS1 in binding studies, and do not specifically alter ESS1‐dependent splicing in vitro . Together, these studies demonstrate that hnRNP‐L is the primary protein through which CD45 exon 4 silencing is mediated by the regulatory sequence ESS1.