Widespread autogenous mRNA-protein interactions detected by CLIP-seq

Thomas H. Kapral, Fiona Farnhammer, Weihao Zhao, Zhi J. Lu, Bojan Zagrovic (Corresponding author)

Publications: Contribution to journalArticlePeer Reviewed

Abstract

Autogenous interactions between mRNAs and the proteins they encode are implicated in cellular feedback-loop regulation, but their extent and mechanistic foundation are unclear. It was recently hypothesized that such interactions may be common, reflecting the role of intrinsic nucleobase-amino acid affinities in shaping the genetic code's structure. Here we analyze a comprehensive set of CLIP-seq experiments involving multiple protocols and report on widespread autogenous interactions across different organisms. Specifically, 230 of 341 (67%) studied RNA-binding proteins (RBPs) interact with their own mRNAs, with a heavy enrichment among high-confidence hits and a preference for coding sequence binding. We account for different confounding variables, including physical (overexpression and proximity during translation), methodological (difference in CLIP protocols, peak callers and cell types) and statistical (treatment of null backgrounds). In particular, we demonstrate a high statistical significance of autogenous interactions by sampling null distributions of fixed-margin interaction matrices. Furthermore, we study the dependence of autogenous binding on the presence of RNA-binding motifs and structured domains in RBPs. Finally, we show that intrinsic nucleobase-amino acid affinities favor co-aligned binding between mRNA coding regions and the proteins they encode. Our results suggest a central role for autogenous interactions in RBP regulation and support the possibility of a fundamental connection between coding and binding.

Original languageEnglish
Pages (from-to)9984-9999
Number of pages16
JournalNucleic Acids Research
Volume50
Issue number17
DOIs
Publication statusPublished - 23 Sept 2022

Austrian Fields of Science 2012

  • 106023 Molecular biology

Fingerprint

Dive into the research topics of 'Widespread autogenous mRNA-protein interactions detected by CLIP-seq'. Together they form a unique fingerprint.

Cite this