MicroRNA binding sites in the coding region of mRNAs: Extending the repertoire of post‐transcriptional gene regulation

Abstract

It is well established that microRNAs (miRNAs) induce mRNA degradation by binding to 3' untranslated regions (UTRs). The functionality of sites in the coding domain sequence (CDS), on the other hand, remains under discussion. Such sites have limited impact on target mRNA abundance and recent work suggests that miRNAs bind in the CDS to inhibit translation. What then could be the regulatory benefits of translation inhibition through CDS targeting compared to mRNA degradation following 3' UTR binding? We propose that these domain-dependent effects serve to diversify the functional repertoire of post-transcriptional gene expression control. Possible regulatory benefits may include tuning the time-scale and magnitude of post-transcriptional regulation, regulating protein abundance depending on or independently of the cellular state, and regulation of the protein abundance of alternative splice variants. Finally, we review emerging evidence that these ideas may generalize to RNA-binding proteins beyond miRNAs and Argonaute proteins.

miR-23∼27∼24 clusters control effector T cell differentiation and function

“…4 D). Although most of the miRNA studies to date have been focused on the regulatory effect of miRNAs in the 3′ UTR of the target genes, it was well documented that miRNAs could also inhibit their target protein translation potentially through interfering with ribosome movement (Hausser et al, 2013;Brümmer and Hausser, 2014). Our luciferase reporter results confirmed that IL-4 is indeed a direct target of miR-24.…”

Cupid: simultaneous reconstruction of microRNA-target and ceRNA networks

“…It is important to note that while our results were based on analyses of reference 39 UTR targeting, recent work (Sandberg et al 2008;Brummer and Hausser 2014) suggests that both alternative polyadenylation and miRNA targeting outside of 39 UTRs may alter miRNA regulation to pathophysiological effects. Incorporating these lines of evidence may help further our understanding of miRNA regulation, and we believe that these challenges can be addressed using current technology.…”

“…For example, statistical evidence suggests that expression profiles of ESR1-regulating miRNAs are predictive of variability in the coupling between ESR1 mRNA and protein-expression profiles. Moreover, a study focusing on the ability of individual miRNA to predict coupling of target mRNA and protein-expression profiles may help identify miRNAs that primarily regulate translation and those that regulate mRNA destabilization (Brummer and Hausser 2014).…”

TmiRUSite and TmiROSite scripts: searching for mRNA fragments with miRNA binding sites with encoded amino acid residues

“…They participate in translation repression [2]. Previously, miRNA binding sites were predicted only at the 3'UTR [3], but recently it is known that these sites are also located at the 5׳- untranslated regions (5׳UTRs) [4] and coding sequences (CDSs) of mRNAs [5]. Therefore, it is of interest to identify miRNA encoded oligo-peptides that are conserved across evolutionary distance.…”