Regulation of vertebrate nervous system alternative splicing and development by an SR-related protein.
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.
Calarco
John A
JA
Banting and Best Department of Medical Research, Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, 160 College Street, Toronto, Ontario M5S 3E1, Canada.
Superina
Simone
S
O'Hanlon
Dave
D
Gabut
Mathieu
M
Raj
Bushra
B
Pan
Qun
Q
Skalska
Ursula
U
Clarke
Laura
L
Gelinas
Danielle
D
van der Kooy
Derek
D
Zhen
Mei
M
Ciruna
Brian
B
Blencowe
Benjamin J
BJ
D017398:Alternative Splicing; D000818:Animals; D001921:Brain / Q000166:cytology; D002454:Cell Differentiation; D002460:Cell Line; D006801:Humans; D051379:Mice; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000166:cytology; D009687:Nuclear Proteins / Q000737:chemistry / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D000068103:Serine-Arginine Splicing Factors
D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D016601:RNA-Binding Proteins; C543899:nSR100 protein, mouse; D000068103:Serine-Arginine Splicing Factors