The mechanism of micro-RNA-mediated translation repression is determined by the promoter of the target gene

Kong, Y. W. et al. (2008) The mechanism of micro-RNA-mediated translation repression is determined by the promoter of the target gene. Proceedings of the National Academy of Sciences of the United States of America, 105(26), pp. 8866-8871. (doi: 10.1073/pnas.0800650105) (PMID:18579786) (PMCID:PMC2449332)

Full text not currently available from Enlighten.

Abstract

MicroRNAs (miRNAs) are noncoding RNAs that base pair imperfectly to homologous regions in target mRNAs and negatively influence the synthesis of the corresponding proteins. Repression is mediated by a number of mechanisms, one of which is the direct inhibition of protein synthesis. Surprisingly, previous studies have suggested that two mutually exclusive mechanisms exist, one acting at the initiation phase of protein synthesis and the other at a postinitiation event. Here, we resolve this apparent dichotomy by demonstrating that the promoter used to transcribe the mRNA influences the type of miRNA-mediated translational repression. Transcripts derived from the SV40 promoter that contain let-7 target sites in their 3′ UTRs are repressed at the initiation stage of translation, whereas essentially identical mRNAs derived from the TK promoter are repressed at a postinitiation step. We also show that there is a miR-34 target site within the 3′ UTR of c-myc mRNA and that promoter dependency is also true for this endogenous 3′ UTR. Overall, these data establish a link between the nuclear history of an mRNA and the mechanism of miRNA-mediated translational regulation in the cytoplasm.

Item Type:Articles
Additional Information:Thisworkwas supported by grants from the Biotechnology and Biological Sciences Research Council (to Y.W.K., I.G.C., T.L.H., P.G.G., and H.C.D.), the Wellcome Trust (to K.A.S., M.S., H.A.M.), and the Leukaemia Research Fund (K.H.). M.B. holds a Biotechnology and Biological Sciences Research Council David Phillips Fellowship.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Bushell, Professor Martin
Authors: Kong, Y. W., Cannell, I. G., de Moor, C. H., Hill, K., Garside, P. G., Hamilton, T. L., Meijer, H. A., Dobbyn, H. C., Stoneley, M., Spriggs, K. A., Willis, A. E., and Bushell, M.
College/School:College of Medical Veterinary and Life Sciences > School of Cancer Sciences
Journal Name:Proceedings of the National Academy of Sciences of the United States of America
Publisher:National Academy of Sciences
ISSN:0027-8424
ISSN (Online):1091-6490
Published Online:28 June 2008

University Staff: Request a correction | Enlighten Editors: Update this record