A large-scale binding and functional map of human RNA-binding proteins

• Published in: Nature (London) 2020-07, Vol.583 (7818), p.711-719
• Main Authors: Van Nostrand, Eric L., Freese, Peter, Pratt, Gabriel A., Wang, Xiaofeng, Wei, Xintao, Xiao, Rui, Blue, Steven M., Chen, Jia-Yu, Cody, Neal A. L., Dominguez, Daniel, Olson, Sara, Sundararaman, Balaji, Zhan, Lijun, Bazile, Cassandra, Bouvrette, Louis Philip Benoit, Bergalet, Julie, Duff, Michael O., Garcia, Keri E., Gelboin-Burkhart, Chelsea, Hochman, Myles, Lambert, Nicole J., Li, Hairi, McGurk, Michael P., Nguyen, Thai B., Palden, Tsultrim, Rabano, Ines, Sathe, Shashank, Stanton, Rebecca, Su, Amanda, Wang, Ruth, Yee, Brian A., Zhou, Bing, Louie, Ashley L., Aigner, Stefan, Fu, Xiang-Dong, Lécuyer, Eric, Burge, Christopher B., Graveley, Brenton R., Yeo, Gene W.
• Format: Article
• Language: English
• Subjects: 13/106; 13/109; 13/89; 14/1; 45; 45/15; 45/44; 45/91; 631/208/212/2019; 631/337/1645/1946; Alternative Splicing - genetics; Analysis; Base Sequence; Binding Sites; Cell Line; Chromatin; Chromatin - genetics; Chromatin - metabolism; Chromosome mapping; Computational biology; Databases, Genetic; Datasets; DNA binding proteins; Encyclopedias; Female; Gene expression; Gene Knockdown Techniques; Gene mapping; Genomes; Humanities and Social Sciences; Humans; Intracellular Space - genetics; Localization; Male; Mapping; Methods; multidisciplinary; Polyadenylation; Post-transcription; Protein Binding; Proteins; Regulatory sequences; Ribonucleic acid; RNA; RNA, Messenger - chemistry; RNA, Messenger - genetics; RNA, Messenger - metabolism; RNA-binding protein; RNA-Binding Proteins - chemistry; RNA-Binding Proteins - genetics; RNA-Binding Proteins - metabolism; Science; Science (multidisciplinary); Splicing; Stability; Substrate Specificity; Transcriptome - genetics
• ISSN: 0028-0836; 1476-4687; 1476-4687
• DOI: 10.1038/s41586-020-2077-3

Many proteins regulate the expression of genes by binding to specific regions encoded in the genome 1 . Here we introduce a new data set of RNA elements in the human genome that are recognized by RNA-binding proteins (RBPs), generated as part of the Encyclopedia of DNA Elements (ENCODE) project phase III. This class of regulatory elements functions only when transcribed into RNA, as they serve as the binding sites for RBPs that control post-transcriptional processes such as splicing, cleavage and polyadenylation, and the editing, localization, stability and translation of mRNAs. We describe the mapping and characterization of RNA elements recognized by a large collection of human RBPs in K562 and HepG2 cells. Integrative analyses using five assays identify RBP binding sites on RNA and chromatin in vivo, the in vitro binding preferences of RBPs, the function of RBP binding sites and the subcellular localization of RBPs, producing 1,223 replicated data sets for 356 RBPs. We describe the spectrum of RBP binding throughout the transcriptome and the connections between these interactions and various aspects of RNA biology, including RNA stability, splicing regulation and RNA localization. These data expand the catalogue of functional elements encoded in the human genome by the addition of a large set of elements that function at the RNA level by interacting with RBPs. A combination of five assays is used to produce a catalogue of RNA elements to which RNA-binding proteins bind in human cells.