title: The VEGF IRESes are differentially susceptible to translation inhibition by miR-16.
abstract: Experiments with EMCV (Encephalomyocarditis virus) internal ribosome entry sites (IRESes) have shown that microRNAs (miRs) are unable to inhibit IRES driven translation. However, it is accepted that miRs can inhibit translation through multiple mechanisms, only some of which require interaction with the 5' cap structure. In this report, we first validate the targeting of miR-16 to a predicted binding site in the VEGF 3'UTR. We developed a series of experiments to ascertain whether or not miR-16 can inhibit translation of transcripts driven by either of the VEGF IRESes. Our results indicate that cellular IRESes can be classified as both sensitive and insensitive to miR control. While VEGF IRES-A activity was not altered by miR-16 targeting to the 3'UTR, IRES-B was susceptible to miR-16 inhibition. Taken together with previous results that show that IRES-B selectively translates the CUG initiated VEGF-121 isoform, we can conclude that the existence of two differentially susceptible IRESes in the VEGF 5'UTR leads to even more complex regulatory control of VEGF isoform production. This study demonstrates for the first time the inhibition of cellular IRES driven translation by a miR.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, Toulouse, France.
authors.forename: Zeïneb S
authors.initials: ZS
authors.lastname: Karaa
authors.forename: Jason S
authors.initials: JS
authors.lastname: Iacovoni
authors.forename: Amandine
authors.initials: A
authors.lastname: Bastide
authors.forename: Eric
authors.initials: E
authors.lastname: Lacazette
authors.forename: Christian
authors.initials: C
authors.lastname: Touriol
authors.forename: Hervé
authors.initials: H
authors.lastname: Prats
mesh_terms: D020413:3' Untranslated Regions / Q000378:metabolism*; D001665:Binding Sites; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism*; D014176:Protein Biosynthesis / Q000235:genetics*; D012270:Ribosomes / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*
chemical_list: D020413:3' Untranslated Regions; C505362:MIRN16 microRNA, human; D035683:MicroRNAs; D042461:Vascular Endothelial Growth Factor A