A compendium of RNA-binding motifs for decoding gene regulation

被引:1145
作者
Ray, Debashish [1 ]
Kazan, Hilal [2 ]
Cook, Kate B. [3 ]
Weirauch, Matthew T. [1 ]
Najafabadi, Hamed S. [1 ,4 ]
Li, Xiao [3 ]
Gueroussov, Serge [3 ]
Albu, Mihai [1 ]
Zheng, Hong [1 ]
Yang, Ally [1 ]
Na, Hong [1 ]
Irimia, Manuel [1 ]
Matzat, Leah H. [5 ]
Dale, Ryan K. [5 ]
Smith, Sarah A. [6 ]
Yarosh, Christopher A. [6 ]
Kelly, Seth M. [7 ]
Nabet, Behnam [6 ]
Mecenas, Desirea [8 ,9 ]
Li, Weimin [10 ]
Laishram, Rakesh S. [10 ]
Qiao, Mei [11 ]
Lipshitz, Howard D. [3 ]
Piano, Fabio [8 ,9 ]
Corbett, Anita H. [7 ]
Carstens, Russ P. [6 ]
Frey, Brendan J. [4 ]
Anderson, Richard A. [10 ]
Lynch, Kristen W. [6 ]
Penalva, Luiz O. F. [11 ]
Lei, Elissa P. [5 ]
Fraser, Andrew G. [1 ,3 ]
Blencowe, Benjamin J. [1 ,3 ]
Morris, Quaid D. [1 ,2 ,3 ,4 ]
Hughes, Timothy R. [1 ,3 ]
机构
[1] Univ Toronto, Donnelly Ctr, Toronto, ON M5S 3E1, Canada
[2] Univ Toronto, Dept Comp Sci, Toronto, ON M5S 2E4, Canada
[3] Univ Toronto, Dept Mol Genet, Toronto, ON M5S 1A8, Canada
[4] Univ Toronto, Dept Elect & Comp Engn, Toronto, ON M5S 3G4, Canada
[5] NIDDK, Lab Cellular & Dev Biol, NIH, Bethesda, MD 20892 USA
[6] Univ Penn, Perelman Sch Med, Dept Med, Philadelphia, PA 19104 USA
[7] Emory Univ, Sch Med, Dept Biochem, Atlanta, GA 30322 USA
[8] NYU, Dept Biol, New York, NY 10003 USA
[9] NYU, Ctr Genom & Syst Biol, New York, NY 10003 USA
[10] Univ Wisconsin, Sch Med & Publ Hlth, Mol & Cellular Pharmacol Program, Madison, WI 53706 USA
[11] UTHSCSA, Childrens Canc Res Inst, San Antonio, TX 78229 USA
基金
加拿大自然科学与工程研究理事会;
关键词
PRE-MESSENGER-RNA; GENOME-WIDE ANALYSIS; TRANSCRIPTION FACTORS; SPLICING REGULATOR; PROTEINS; SPECIFICITIES; RECOGNITION; REVEALS; FAMILY; CODE;
D O I
10.1038/nature12311
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];
摘要
RNA-binding proteins are key regulators of gene expression, yet only a small fraction have been functionally characterized. Here we report a systematic analysis of the RNA motifs recognized by RNA-binding proteins, encompassing 205 distinct genes from 24 diverse eukaryotes. The sequence specificities of RNA-binding proteins display deep evolutionary conservation, and the recognition preferences for a large fraction of metazoan RNA-binding proteins can thus be inferred from their RNA-binding domain sequence. The motifs that we identify in vitro correlate well with in vivo RNA-binding data. Moreover, we can associate them with distinct functional roles in diverse types of post-transcriptional regulation, enabling new insights into the functions of RNA-binding proteins both in normal physiology and in human disease. These data provide an unprecedented overview of RNA-binding proteins and their targets, and constitute an invaluable resource for determining post-transcriptional regulatory mechanisms in eukaryotes.
引用
收藏
页码:172 / 177
页数:6
相关论文
共 47 条
[1]
The RNA-binding protein SUP-12 controls muscle-specific splicing of the ADF/cofilin pre-mRNA in C. elegans [J].
Anyanful, A ;
Ono, K ;
Johnsen, RC ;
Ly, H ;
Jensen, V ;
Baillie, DL ;
Ono, S .
JOURNAL OF CELL BIOLOGY, 2004, 167 (04) :639-647
[2]
Sequence-specific binding of single-stranded RNA: is there a code for recognition? [J].
Auweter, Sigrid D. ;
Oberstrass, Florian C. ;
Allain, Frederic H. -T. .
NUCLEIC ACIDS RESEARCH, 2006, 34 (17) :4943-4959
[3]
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
[4]
Variation in homeodomain DNA binding revealed by high-resolution analysis of sequence preferences [J].
Berger, Michael F. ;
Badis, Gwenael ;
Gehrke, Andrew R. ;
Talukder, Shaheynoor ;
Philippakis, Anthony A. ;
Pena-Castillo, Lourdes ;
Alleyne, Trevis M. ;
Mnaimneh, Sanie ;
Botvinnik, Olga B. ;
Chan, Esther T. ;
Khalid, Faiqua ;
Zhang, Wen ;
Newburger, Daniel ;
Jaeger, Savina A. ;
Morris, Quaid D. ;
Bulyk, Martha L. ;
Hughes, Timothy R. .
CELL, 2008, 133 (07) :1266-1276
[5]
Universal protein-binding microarrays for the comprehensive characterization of the DNA-binding specificities of transcription factors [J].
Berger, Michael F. ;
Bulyk, Martha L. .
NATURE PROTOCOLS, 2009, 4 (03) :393-411
[6]
The quaking family of RNA-binding proteins Coordinators of the cell cycle and differentiation [J].
Biedermann, Bjoern ;
Hotz, Hans-Rudolf ;
Ciosk, Rafal .
CELL CYCLE, 2010, 9 (10) :1929-1933
[7]
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
[8]
Conservation of an RNA regulatory map between Drosophila and mammals [J].
Brooks, Angela N. ;
Yang, Li ;
Duff, Michael O. ;
Hansen, Kasper D. ;
Park, Jung W. ;
Dudoit, Sandrine ;
Brenner, Steven E. ;
Graveley, Brenton R. .
GENOME RESEARCH, 2011, 21 (02) :193-202
[9]
RNA-BINDING SPECIFICITY OF HNRNP A1 - SIGNIFICANCE OF HNRNP A1 HIGH-AFFINITY BINDING-SITES IN PRE-MESSENGER-RNA SPLICING [J].
BURD, CG ;
DREYFUSS, G .
EMBO JOURNAL, 1994, 13 (05) :1197-1204
[10]
Insights into RNA Biology from an Atlas of Mammalian mRNA-Binding Proteins [J].
Castello, Alfredo ;
Fischer, Bernd ;
Eichelbaum, Katrin ;
Horos, Rastislav ;
Beckmann, Benedikt M. ;
Strein, Claudia ;
Davey, Norman E. ;
Humphreys, David T. ;
Preiss, Thomas ;
Steinmetz, Lars M. ;
Krijgsveld, Jeroen ;
Hentze, Matthias W. .
CELL, 2012, 149 (06) :1393-1406