Analysis of CDS-located miRNA target sites suggests that they can effectively inhibit translation

Abstract

Most of what is presently known about how miRNAs regulate gene expression comes from studies that characterized the regulatory effect of miRNA binding sites located in the 39 untranslated regions (UTR) of mRNAs. In recent years, there has been increasing evidence that miRNAs also bind in the coding region (CDS), but the implication of these interactions remains obscure because they have a smaller impact on mRNA stability compared with miRNA-target interactions that involve 39 UTRs. Here we show that miRNA-complementary sites that are located in both CDS and 39-UTRs are under selection pressure and share the same sequence and structure properties. Analyzing recently published data of ribosomeprotected fragment profiles upon miRNA transfection from the perspective of the location of miRNA-complementary sites, we find that sites located in the CDS are most potent in inhibiting translation, while sites located in the 39 UTR are more efficient at triggering mRNA degradation. Our study suggests that miRNAs may combine targeting of CDS and 39 UTR to flexibly tune the time scale and magnitude of their post-transcriptional regulatory effects. © 2013, Published by Cold Spring Harbor Laboratory Press.