RT Journal
A1 Brooks, Angela N.
A1 Yang, Li
A1 Duff, Michael O.
A1 Hansen, Kasper D.
A1 Park, Jung W.
A1 Dudoit, Sandrine
A1 Brenner, Steven E.
A1 Graveley, Brenton R.
T1 Conservation of an RNA regulatory map between Drosophila and mammals
JF Genome Research 
JO Genome Research 
YR 2011 
FD February 01 
VO 21 
IS 2 
SP 193 
OP 202 
DO 10.1101/gr.108662.110 
UL http://genome.cshlp.org/content/21/2/193.abstract 
AB Alternative splicing is generally controlled by proteins that bind directly to regulatory sequence elements and either activate or repress splicing of adjacent splice sites in a target pre-mRNA. Here, we have combined RNAi and mRNA-seq to identify exons that are regulated by Pasilla (PS), the Drosophila melanogaster ortholog of mammalian NOVA1 and NOVA2. We identified 405 splicing events in 323 genes that are significantly affected upon depletion of ps, many of which were annotated as being constitutively spliced. The sequence regions upstream and within PS-repressed exons and downstream from PS-activated exons are enriched for YCAY repeats, and these are consistent with the location of these motifs near NOVA-regulated exons in mammals. Thus, the RNA regulatory map of PS and NOVA1/2 is highly conserved between insects and mammals despite the fact that the target gene orthologs regulated by PS and NOVA1/2 are almost entirely nonoverlapping. This observation suggests that the regulatory codes of individual RNA binding proteins may be nearly immutable, yet the regulatory modules controlled by these proteins are highly evolvable.