PUBLICATION
Evolution of Nova-Dependent Splicing Regulation in the Brain
- Authors
- Jelen, N., Ule, J., Ivin, M., and Darnell, R.B.
- ID
- ZDB-PUB-071023-15
- Date
- 2007
- Source
- PLoS Genetics 3(10): 1838-1847 (Journal)
- Registered Authors
- Keywords
- Zebrafish, Chickens, Alternative splicing, Mammalian genomics, RNA splicing, Sequence motif analysis, Sequence alignment, Sequence analysis
- MeSH Terms
-
- Alternative Splicing*
- Amyloidogenic Proteins/genetics*
- Animals
- Antigens, Neoplasm/genetics*
- Brain/metabolism*
- Chickens
- Evolution, Molecular
- Humans
- Mice
- Models, Biological
- Multigene Family
- Nerve Tissue Proteins/genetics*
- Opossums
- RNA-Binding Proteins/genetics*
- Species Specificity
- Xenopus
- Zebrafish
- Zebrafish Proteins/genetics*
- PubMed
- 17937501 Full text @ PLoS Genet.
Citation
Jelen, N., Ule, J., Ivin, M., and Darnell, R.B. (2007) Evolution of Nova-Dependent Splicing Regulation in the Brain. PLoS Genetics. 3(10):1838-1847.
Abstract
A large number of alternative exons are spliced with tissue-specific patterns, but little is known about how such patterns have evolved. Here, we study the conservation of the neuron-specific splicing factors Nova1 and Nova2 and of the alternatively spliced exons they regulate in mouse brain. Whereas Nova RNA binding domains are 94% identical across vertebrate species, Nova-dependent splicing silencer and enhancer elements (YCAY clusters) show much greater divergence, as less than 50% of mouse YCAY clusters are conserved at orthologous positions in the zebrafish genome. To study the relation between the evolution of tissue-specific splicing and YCAY clusters, we compared the brain-specific splicing of Nova-regulated exons in zebrafish, chicken, and mouse. The presence of YCAY clusters in lower vertebrates invariably predicted conservation of brain-specific splicing across species, whereas their absence in lower vertebrates correlated with a loss of alternative splicing. We hypothesize that evolution of Nova-regulated splicing in higher vertebrates proceeds mainly through changes in cis-acting elements, that tissue-specific splicing might in some cases evolve in a single step corresponding to evolution of a YCAY cluster, and that the conservation level of YCAY clusters relates to the functions encoded by the regulated RNAs.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping