Conservation of an RNA regulatory map between Drosophila and mammals

Angela N. Brooks, Li Yang, Michael O. Duff, Kasper D. Hansen, Jung W. Park, Sandrine Dudoit, Steven E. Brenner, Brenton R. Graveley

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)193-202
Number of pages10
JournalGenome research
Volume21
Issue number2
DOIs
StatePublished - Feb 2011
Externally publishedYes

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Fingerprint Dive into the research topics of 'Conservation of an RNA regulatory map between Drosophila and mammals'. Together they form a unique fingerprint.

Cite this