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Alternative splicing as a mechanism for signal‐induced gene regulation
Author(s) -
Lynch Kristen Wood
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a96-e
Subject(s) - rna splicing , exon , exon skipping , alternative splicing , exonic splicing enhancer , gene , biology , intron , genetics , microbiology and biotechnology , rna binding protein , rna
Alternative splicing is emerging as a prevalent mechanism for altering protein expression in response to environmental cues. We have recently found that, upon activation by antigen, T cells undergo coordinated changes in alternative splicing. As a model system to explore the mechanisms of signal‐induced alternative splicing in T cells my group has been studying the regulated splicing of the CD45 gene. The CD45 gene, which encodes a transmembrane protein tyrosine phosphatase, has three variable exons that are differentially excluded in T cells upon antigen challenge. An exonic splicing silencer element (ESS1) exists in each of the CD45 variable exons, and also exhibits homology to exons of other signal‐responsive genes. Using a variety of biochemical approaches we have identified a complex of hnRNP proteins that associates specifically with the ESS1 sequence and promotes exon skipping. Strikingly, repression of splicing by the ESS1‐bound complex appears to occur by a mechanism distinct from those previously described for exon skipping. Moreover, while all of the proteins within the ESS1‐bound complex are present in resting cells, only a suboptimal subset bind to the ESS1 prior to stimulation. The mechanism of this differential RNA association is currently being investigated.