New computational model for miRNA-mediated repression reveals novel regulatory roles of miRNA bindings inside the coding region

Shaked Bergman, Alon DIament, Tamir Tuller*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Motivation: MicroRNAs (miRNAs) are short (∼24nt), non-coding RNAs, which downregulate gene expression in many species and physiological processes. Many details regarding the mechanism which governs miRNA-mediated repression continue to elude researchers. Results: We elucidate the interplay between the coding sequence and the 3′UTR, by using elastic net regularization and incorporating translation-related features to predict miRNA-mediated repression. We find that miRNA binding sites at the end of the coding sequence contribute to repression, and that weak binding sites are linked to effective de-repression, possibly as a result of competing with stronger binding sites. Furthermore, we propose a recycling model for miRNAs dissociated from the open reading frame (ORF) by traversing ribosomes, explaining the observed link between increased ribosome density/traversal speed and increased repression. We uncover a novel layer of interaction between the coding sequence and the 3′UTR (untranslated region) and suggest the ORF has a larger role than previously thought in the mechanism of miRNA-mediated repression.

Original languageEnglish
Pages (from-to)5398-5404
Number of pages7
JournalBioinformatics
Volume36
Issue number22-23
DOIs
StatePublished - 1 Dec 2020

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