Conservation of an RNA regulatory map between Drosophila and mammals

被引:155
作者
Brooks, Angela N. [1 ]
Yang, Li [2 ]
Duff, Michael O. [2 ,3 ]
Hansen, Kasper D. [4 ]
Park, Jung W. [2 ,3 ]
Dudoit, Sandrine [4 ,5 ]
Brenner, Steven E. [1 ,6 ]
Graveley, Brenton R. [2 ,3 ]
机构
[1] Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA
[2] Univ Connecticut, Ctr Hlth, Dept Genet & Dev Biol, Farmington, CT 06030 USA
[3] Univ Connecticut, Ctr Hlth, Univ Connecticut Stem Cell Inst, Farmington, CT 06030 USA
[4] Univ Calif Berkeley, Sch Publ Hlth, Div Biostat, Berkeley, CA 94720 USA
[5] Univ Calif Berkeley, Dept Stat, Berkeley, CA 94720 USA
[6] Univ Calif Berkeley, Dept Plant & Microbial Biol, Berkeley, CA 94720 USA
基金
美国国家科学基金会;
关键词
GENOME-WIDE ANALYSIS; DEPENDENT SPLICING REGULATION; REVEALS; SEQUENCE; BINDING; BRAIN; CODE; INTERFERENCE; INSIGHTS; ELEMENTS;
D O I
10.1101/gr.108662.110
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:193 / 202
页数:10
相关论文
共 41 条
[1]   The genome sequence of Drosophila melanogaster [J].
Adams, MD ;
Celniker, SE ;
Holt, RA ;
Evans, CA ;
Gocayne, JD ;
Amanatides, PG ;
Scherer, SE ;
Li, PW ;
Hoskins, RA ;
Galle, RF ;
George, RA ;
Lewis, SE ;
Richards, S ;
Ashburner, M ;
Henderson, SN ;
Sutton, GG ;
Wortman, JR ;
Yandell, MD ;
Zhang, Q ;
Chen, LX ;
Brandon, RC ;
Rogers, YHC ;
Blazej, RG ;
Champe, M ;
Pfeiffer, BD ;
Wan, KH ;
Doyle, C ;
Baxter, EG ;
Helt, G ;
Nelson, CR ;
Miklos, GLG ;
Abril, JF ;
Agbayani, A ;
An, HJ ;
Andrews-Pfannkoch, C ;
Baldwin, D ;
Ballew, RM ;
Basu, A ;
Baxendale, J ;
Bayraktaroglu, L ;
Beasley, EM ;
Beeson, KY ;
Benos, PV ;
Berman, BP ;
Bhandari, D ;
Bolshakov, S ;
Borkova, D ;
Botchan, MR ;
Bouck, J ;
Brokstein, P .
SCIENCE, 2000, 287 (5461) :2185-2195
[2]   Deciphering the splicing code [J].
Barash, Yoseph ;
Calarco, John A. ;
Gao, Weijun ;
Pan, Qun ;
Wang, Xinchen ;
Shai, Ofer ;
Blencowe, Benjamin J. ;
Frey, Brendan J. .
NATURE, 2010, 465 (7294) :53-59
[3]   Next generation software for functional trend analysis [J].
Berriz, Gabriel F. ;
Beaver, John E. ;
Cenik, Can ;
Tasan, Murat ;
Roth, Frederick P. .
BIOINFORMATICS, 2009, 25 (22) :3043-3044
[4]   Global analysis of positive and negative pre-mRNA splicing regulators in Drosophila [J].
Blanchette, M ;
Green, RE ;
Brenner, SE ;
Rio, DC .
GENES & DEVELOPMENT, 2005, 19 (11) :1306-1314
[5]   Genome-wide analysis reveals an unexpected function for the Drosophila splicing factor U2AF50 in the nuclear export of intronless mRNAs [J].
Blanchette, M ;
Labourier, E ;
Green, RE ;
Brenner, SE ;
Rio, DC .
MOLECULAR CELL, 2004, 14 (06) :775-786
[6]   Genome-wide Analysis of Alternative Pre-mRNA Splicing and RNA-Binding Specificities of the Drosophila hnRNP A/B Family Members [J].
Blanchette, Marco ;
Green, Richard E. ;
MacArthur, Stewart ;
Brooks, Angela N. ;
Brenner, Steven E. ;
Eisen, Michael B. ;
Rio, Donald C. .
MOLECULAR CELL, 2009, 33 (04) :438-449
[7]  
CELNIKER SE, 2002, GENOME BIOL, V0003
[8]   Mechanisms of alternative splicing regulation: insights from molecular and genomics approaches [J].
Chen, Mo ;
Manley, James L. .
NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2009, 10 (11) :741-754
[9]  
Chiaromonte F, 2002, Pac Symp Biocomput, P115
[10]   Evolution of nova-dependent splicing regulation in the brain [J].
Jelen, Nejc ;
Ule, Jernej ;
Zivin, Marko ;
Darnell, Robert B. .
PLOS GENETICS, 2007, 3 (10) :1838-1847