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

@article{citeulike:2939158, 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. 10.1073/pnas.0800650105}, author = {Kong, Yi W. and Cannell, Ian G. and de Moor, Cornelia H. and Hill, Kirsti and Garside, Paul G. and Hamilton, Tiffany L. and Meijer, Hedda A. and Dobbyn, Helen C. and Stoneley, Mark and Spriggs, Keith A. and Willis, Anne E. and Bushell, Martin }, citeulike-article-id = {2939158}, doi = {http://dx.doi.org/10.1073/pnas.0800650105}, journal = {Proceedings of the National Academy of Sciences}, keywords = {microrna, promoter, regulation}, month = {June}, pages = {0800650105+}, posted-at = {2008-06-30 11:35:03}, priority = {2}, title = {The mechanism of micro-RNA-mediated translation repression is determined by the promoter of the target gene}, url = {http://dx.doi.org/10.1073/pnas.0800650105}, year = {2008} }

TY - JOUR ID - citeulike:2939158 L3 - citeulike-article-id:2939158 N2 - 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. 10.1073/pnas.0800650105 JF - Proceedings of the National Academy of Sciences TI - The mechanism of micro-RNA-mediated translation repression is determined by the promoter of the target gene SP - 0800650105 KW - microrna KW - promoter KW - regulation AU - Kong, Yi AU - Cannell, Ian AU - de Moor, Cornelia AU - Hill, Kirsti AU - Garside, Paul AU - Hamilton, Tiffany AU - Meijer, Hedda AU - Dobbyn, Helen AU - Stoneley, Mark AU - Spriggs, Keith AU - Willis, Anne AU - Bushell, Martin PY - 2008/06/25/ UR - http://dx.doi.org/10.1073/pnas.0800650105 ER -