HnRNP L represses exon splicing via a regulated exonic splicing silencer
| Autor: | Caryn R. Rothrock, Amy E. House, Kristen W. Lynch |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2005 |
| Předmět: |
RNA Splicing
Molecular Sequence Data Exonic splicing enhancer Biology Heterogeneous ribonucleoprotein particle environment and public health General Biochemistry Genetics and Molecular Biology Article Splicing factor Exon Heterogeneous-Nuclear Ribonucleoprotein L Silencer Elements Transcriptional Animals Humans Molecular Biology Exonic splicing silencer General Immunology and Microbiology Base Sequence General Neuroscience Alternative splicing Exons Molecular biology Repressor Proteins RNA splicing Leukocyte Common Antigens Minigene Polypyrimidine Tract-Binding Protein |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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