Research ArticleMICRORNAs

Signaling by p38 MAPK Stimulates Nuclear Localization of the Microprocessor Component p68 for Processing of Selected Primary MicroRNAs

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Science Signaling  12 Mar 2013:
Vol. 6, Issue 266, pp. ra16
DOI: 10.1126/scisignal.2003706

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Promoting MicroRNA Production

MicroRNAs (miRNAs) are small noncoding RNAs that target specific mRNAs for degradation or block their translation, thus leading to knockdown of given gene products. Posttranscriptional generation of miRNAs requires the nuclear processing of primary miRNAs (pri-miRNAs) by components of the Drosha-containing complex followed by the cytosolic processing of the resulting precursor miRNAs (pre-miRNAs) by the Dicer complex to generate mature miRNAs. Hong et al. found that inhibition of the mitogen-activated protein kinase (MAPK) p38 and its effector kinase MK2 blocked the processing of a subset of pri-miRNAs. In the cytosol, MK2 phosphorylated the Drosha complex component p68, which was required for its translocation to the nucleus for pri-miRNA processing. Inhibition of p38 signaling in cells decreased the production of miR-145, which targets the mRNA encoding c-Myc, resulting in increased c-Myc abundance and enhanced proliferation. Together, these data suggest that p38 MAPK signaling is required for selected miRNA biogenesis by promoting the nuclear localization of p68.

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