PUBLICATION
Regulation of vertebrate nervous system alternative splicing and development by an SR-related protein
- Authors
- Calarco, J.A., Superina, S., O'Hanlon, D., Gabut, M., Raj, B., Pan, Q., Skalska, U., Clarke, L., Gelinas, D., van der Kooy, D., Zhen, M., Ciruna, B., and Blencowe, B.J.
- ID
- ZDB-PUB-090914-41
- Date
- 2009
- Source
- Cell 138(5): 898-910 (Journal)
- Registered Authors
- Ciruna, Brian, Gelinas, Danielle, Superina, Simone
- Keywords
- RNA, MOLNEURO, DEVBIO
- MeSH Terms
-
- Alternative Splicing*
- Animals
- Brain/cytology
- Cell Differentiation
- Cell Line
- Humans
- Mice
- Nerve Tissue Proteins/chemistry
- Nerve Tissue Proteins/genetics
- Nerve Tissue Proteins/metabolism*
- Neurons/cytology
- Nuclear Proteins/chemistry
- Nuclear Proteins/metabolism*
- RNA-Binding Proteins/chemistry
- RNA-Binding Proteins/metabolism*
- Serine-Arginine Splicing Factors
- PubMed
- 19737518 Full text @ Cell
Citation
Calarco, J.A., Superina, S., O'Hanlon, D., Gabut, M., Raj, B., Pan, Q., Skalska, U., Clarke, L., Gelinas, D., van der Kooy, D., Zhen, M., Ciruna, B., and Blencowe, B.J. (2009) Regulation of vertebrate nervous system alternative splicing and development by an SR-related protein. Cell. 138(5):898-910.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping