Jelen, N;
Ule, J;
Zivin, M;
Darnell, RB;
(2007)
Evolution of Nova-dependent splicing regulation in the brain.
PLoS Genet
, 3
(10)
, Article e173. 10.1371/journal.pgen.0030173.
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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.
| Type: | Article |
|---|---|
| Title: | Evolution of Nova-dependent splicing regulation in the brain |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1371/journal.pgen.0030173 |
| Publisher version: | http://dx.doi.org/10.1371/journal.pgen.0030173 |
| Language: | English |
| Additional information: | © 2007 Jelen et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: Supported by the National Institutes of Health (NIH) (R01 NS34389 and NS40955 to RBD) and a GCRC Grant (M01-RR00102) from the National Center for Research Resources at NIH. RBD is an Investigator of the Howard Hughes Medical Institute. |
| Keywords: | *Alternative Splicing 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 |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Department of Neuromuscular Diseases |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1392083 |
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