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Publication : Regulation of vertebrate nervous system alternative splicing and development by an SR-related protein.

First Author  Calarco JA Year  2009
Journal  Cell Volume  138
Issue  5 Pages  898-910
PubMed ID  19737518 Mgi Jnum  J:155499
Mgi Id  MGI:4414616 Doi  10.1016/j.cell.2009.06.012
Citation  Calarco JA, et al. (2009) Regulation of vertebrate nervous system alternative splicing and development by an SR-related protein. Cell 138(5):898-910
abstractText  Alternative splicing is a key process underlying the evolution of increased proteomic and functional complexity and is especially prevalent in the mammalian nervous system. However, the factors and mechanisms governing nervous system-specific alternative splicing are not well understood. Through a genome-wide computational and expression profiling strategy, we have identified a tissue- and vertebrate-restricted Ser/Arg (SR) repeat splicing factor, the neural-specific SR-related protein of 100 kDa (nSR100). We show that nSR100 regulates an extensive network of brain-specific alternative exons enriched in genes that function in neural cell differentiation. nSR100 acts by increasing the levels of the neural/brain-enriched polypyrimidine tract binding protein and by interacting with its target transcripts. Disruption of nSR100 prevents neural cell differentiation in cell culture and in the developing zebrafish. Our results thus reveal a critical neural-specific alternative splicing regulator, the evolution of which has contributed to increased complexity in the vertebrate nervous system.
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