title: 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 3' 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 3' UTRs. Here we show that miRNA-complementary sites that are located in both CDS and 3'-UTRs are under selection pressure and share the same sequence and structure properties. Analyzing recently published data of ribosome-protected 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 3' UTR are more efficient at triggering mRNA degradation. Our study suggests that miRNAs may combine targeting of CDS and 3' UTR to flexibly tune the time scale and magnitude of their post-transcriptional regulatory effects.
authors: Biozentrum, University of Basel and Swiss Institute of Bioinformatics, 4056 Basel, Switzerland. jean.hausser@unibas.ch
authors: Jean
authors: J
authors: Hausser
authors: Afzal Pasha
authors: AP
authors: Syed
authors: Biter
authors: B
authors: Bilen
authors: Mihaela
authors: M
authors: Zavolan
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D001665:Binding Sites; D019295:Computational Biology; D017124:Conserved Sequence; D047108:Embryonic Development; D019143:Evolution, Molecular; D005786:Gene Expression Regulation; D006801:Humans; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D009690:Nucleic Acid Conformation; D016366:Open Reading Frames; D014176:Protein Biosynthesis / Q000235:genetics*; D020871:RNA Stability; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism*; D012641:Selection, Genetic
chemical_list: D020413:3' Untranslated Regions; D035683:MicroRNAs; D012333:RNA, Messenger