Author/Editor		Jelen, Nejc; Ule, Jernej; Živin, Marko; Darnell, Robert B
Title		Evolution of Nova-dependent splicing regulation in the brain
Type		članek
Source		PLoS Genet
Vol. and No.		Letnik 3, št. 10
Publication year		2007
Volume		str. 1838-47
Language		eng
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.
Descriptors		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