Binding specificities of human RNA-binding proteins toward structured and linear RNA sequences

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Jolma , A , Zhang , J , Mondragon , E , Morgunova , E , Kivioja , T , Laverty , K U , Yin , Y , Zhu , F , Bourenkov , G , Morris , Q , Hughes , T R , Maher III , L J & Taipale , J 2020 , ' Binding specificities of human RNA-binding proteins toward structured and linear RNA sequences ' , Genome Research , vol. 30 , no. 7 , pp. 962-973 .

Title: Binding specificities of human RNA-binding proteins toward structured and linear RNA sequences
Author: Jolma, Arttu; Zhang, Jilin; Mondragon, Estefania; Morgunova, Ekaterina; Kivioja, Teemu; Laverty, Kaitlin U.; Yin, Yimeng; Zhu, Fangjie; Bourenkov, Gleb; Morris, Quaid; Hughes, Timothy R.; Maher III, Louis James; Taipale, Jussi
Contributor organization: Research Programs Unit
University of Helsinki
ATG - Applied Tumor Genomics
Doctoral Programme in Integrative Life Science
Department of Pathology
University Management
Jussi Taipale / Principal Investigator
Date: 2020-07
Language: eng
Number of pages: 12
Belongs to series: Genome Research
ISSN: 1088-9051
Abstract: RNA-binding proteins (RBPs) regulate RNA metabolism at multiple levels by affecting splicing of nascent transcripts, RNA folding, base modification, transport, localization, translation, and stability. Despite their central role in RNA function, the RNA-binding specificities of most RBPs remain unknown or incompletely defined. To address this, we have assembled a genome-scale collection of RBPs and their RNA-binding domains (RBDs) and assessed their specificities using high-through-put RNA-SELEX (HTR-SELEX). Approximately 70% of RBPs for which we obtained a motif bound to short linear sequenc-es, whereas similar to 30% preferred structured motifs folding into stem-loops. We also found that many RBPs can bind to multiple distinctly different motifs. Analysis of the matches of the motifs in human genomic sequences suggested novel roles for many RBPs. We found that three cytoplasmic proteins-ZC3H12A, ZC3H12B, and ZC3H12C-bound to motifs resembling the splice donor sequence, suggesting that these proteins are involved in degradation of cytoplasmic viral and/or unspliced transcripts. Structural analysis revealed that the RNA motif was not bound by the conventional C3H1 RNA-binding domain of ZC3H12B. Instead, the RNA motif was bound by the ZC3H12B's PilT N terminus (PIN) RNase domain, revealing a po-tential mechanism by which unconventional RBDs containing active sites or molecule-binding pockets could interact with short, structured RNA molecules. Our collection containing 145 high-resolution binding specificity models for 86 RBPs is the largest systematic resource for the analysis of human RBPs and will greatly facilitate future analysis of the various bi-ological roles of this important class of proteins.
1182 Biochemistry, cell and molecular biology
318 Medical biotechnology
11832 Microbiology and virology
1184 Genetics, developmental biology, physiology
Peer reviewed: Yes
Rights: cc_by_nc
Usage restriction: openAccess
Self-archived version: publishedVersion

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