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Sci Rep. 2012;2:996. doi: 10.1038/srep00996. Epub 2012 Dec 18.

Stability of miRNA 5'terminal and seed regions is correlated with experimentally observed miRNA-mediated silencing efficacy.

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Department of Computational Biology, Graduate School of Frontier Sciences, University of Tokyo , 5-1-5 Kashiwanoha, Kashiwa-shi, Chiba-ken 277-8561, Japan.


MicroRNAs (miRNAs) are key regulators of sequence-specific gene silencing. However, crucial factors that determine the efficacy of miRNA-mediated target gene silencing are poorly understood. Here we mathematized base-pairing stability and showed that miRNAs with an unstable 5' terminal duplex and stable seed-target duplex exhibit strong silencing activity. The results are consistent with the previous findings that an RNA strand with unstable 5' terminal in miRNA duplex easily loads onto the RNA-induced silencing complex (RISC), and miRNA recognizes target mRNAs with seed-complementary sequences to direct posttranscriptional repression. Our results suggested that both the unwinding and target recognition processes of miRNAs could be proficiently controlled by the thermodynamics of base-pairing in protein-free condition. Interestingly, such thermodynamic parameters might be evolutionarily well adapted to the body temperatures of various species.

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