MicroRNAs (miRNAs) guide posttranscriptional repression of mRNAs. Hundreds of miRNAs have been identified but the target identification of mammalian mRNAs is still a difficult task due to a poor understanding of the interaction between miRNAs and the miRNA recognizing element (MRE). In recent research, the importance of the 5' end of the miRNA:MRE duplex has been emphasized and the effect of the tail region addressed, but the role of the central loop has largely remained unexplored. Here we examined the effect of the loop region in miRNA:MRE duplexes and found that the location of the central loop is one of the important factors affecting the efficiency of gene regulation mediated by miRNAs. It was further determined that the addition of a loop score combining both location and size as a new criterion for predicting MREs and their cognate miRNAs significantly decreased the false positive rates and increased the specificity of MRE prediction.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2248708 | PMC |
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0001719 | PLOS |
Nucleic Acids Res
October 2013
Human Genetics Foundation (HuGeF), via Nizza 52, 10126 Torino, Italy, Dipartimento di Biotecnologie, Chimica e Farmacia, Università degli Studi di Siena, Via Fiorentina 1, 53100 Siena, Italy and Siena Biotech, Strada Petriccio Belriguardo 35, Siena, Italy.
The prediction of pairing between microRNAs (miRNAs) and the miRNA recognition elements (MREs) on mRNAs is expected to be an important tool for understanding gene regulation. Here, we show that mRNAs that contain Pumilio recognition elements (PRE) in the proximity of predicted miRNA-binding sites are more likely to form stable secondary structures within their 3'-UTR, and we demonstrated using a PUM1 and PUM2 double knockdown that Pumilio proteins are general regulators of miRNA accessibility. On the basis of these findings, we developed a computational method for predicting miRNA targets that accounts for the presence of PRE in the proximity of seed-match sequences within poorly accessible structures.
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