Shaked Bergman1, Alon Diament1, Tamir Tuller1,2. 1. Department of Biomedical Engineering, Tel-Aviv University, Tel Aviv, Israel. 2. The Sagol School of Neuroscience, Tel-Aviv University, Tel Aviv, Israel.
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. AVAILABILITY: The code is freely available at https://github.com/aescrdni/miRNA_model. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
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. AVAILABILITY: The code is freely available at https://github.com/aescrdni/miRNA_model. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.