Avtor/Urednik | Jelen, Nejc; Ule, Jernej; Živin, Marko; Darnell, Robert B | |
Naslov | Evolution of Nova-dependent splicing regulation in the brain | |
Tip | članek | |
Vir | PLoS Genet | |
Vol. in št. | Letnik 3, št. 10 | |
Leto izdaje | 2007 | |
Obseg | str. 1838-47 | |
Jezik | eng | |
Abstrakt | 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. | |
Deskriptorji | ALTERNATIVE SPLICING ANIMALS ANTIGENS, NEOPLASM BRAIN CHICKENS EVOLUTION, MOLECULAR MICE MODELS, BIOLOGICAL MULTIGENE FAMILY NERVE TISSUE PROTEINS OPOSSUMS RNA-BINDING PROTEINS SPECIES SPECIFICITY XENOPUS ZEBRAFISH |