Conservation of an RNA regulatory map between Drosophila and mammals
- Angela N. Brooks1,7,
- Li Yang2,7,
- Michael O. Duff2,3,
- Kasper D. Hansen4,
- Jung W. Park2,3,
- Sandrine Dudoit4,5,
- Steven E. Brenner1,6,8 and
- Brenton R. Graveley2,3,8
- 1Department of Molecular and Cell Biology, University of California, Berkeley, California 94720, USA;
- 2Department of Genetics and Developmental Biology, University of Connecticut Health Center, Farmington, Connecticut 06030, USA;
- 3University of Connecticut Stem Cell Institute, University of Connecticut Health Center, Farmington, Connecticut 06030, USA;
- 4Division of Biostatistics, School of Public Health, University of California, Berkeley, California 94720, USA;
- 5Department of Statistics, University of California, Berkeley, California 94720, USA;
- 6Department of Plant and Microbial Biology, University of California, Berkeley, California 94720, USA
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↵7 These authors contributed equally to this work.
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.
Footnotes
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↵8 Corresponding authors.
E-mail brenner{at}compbio.berkeley.edu; fax (510) 666-2505.
E-mail graveley{at}neuron.uchc.edu; fax (860) 679-8345.
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[Supplemental material is available for this article. The RNA-sequence data from this study have been submitted to the NCBI Gene Expression Omnibus (http://www.ncbi.nlm.nih.gov/geo) under accession nos. GSM461176-GSM461181.]
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Article published online before print. Article, supplemental material, and publication date are at http://www.genome.org/cgi/doi/10.1101/gr.108662.110.
- Received April 2, 2010.
- Accepted September 30, 2010.
- Copyright © 2011 by Cold Spring Harbor Laboratory Press
Freely available online through the Genome Research Open Access option.
