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

Research output: Journal Publications and ReviewsRGC 21 - Publication in refereed journalpeer-review

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Author(s)

  • Arttu Jolma
  • Jussi Taipale
  • Ekaterina Morgunova
  • Teemu Kivioja
  • Kaitlin U. Laverty
  • Yimeng Yin
  • Fangjie Zhu
  • Gleb Bourenkov
  • Quaid Morris
  • Timothy R. Hughes
  • Louis James Maher
  • Jussi Taipale

Detail(s)

Original languageEnglish
Pages (from-to)962-973
Journal / PublicationGenome Research
Volume30
Issue number7
Online published23 Jul 2020
Publication statusPublished - Jul 2020
Externally publishedYes

Link(s)

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-throughput RNA-SELEX (HTR-SELEX). Approximately 70% of RBPs for which we obtained a motif bound to short linear sequences, whereas ∼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 potential 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 biological roles of this important class of proteins.

Research Area(s)

Citation Format(s)

Binding specificities of human RNA-binding proteins toward structured and linear RNA sequences. / Jolma, Arttu; Zhang, Jilin; Taipale, Jussi et al.
In: Genome Research, Vol. 30, No. 7, 07.2020, p. 962-973.

Research output: Journal Publications and ReviewsRGC 21 - Publication in refereed journalpeer-review

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