Salzman, David W.Nakamura, KotokaNallur, SunithaDookwah, Michelle T.Metheetrairut, ChanatipSlack, FrankWeidhaas, Joanne B.2016-04-012016Salzman, David W., Kotoka Nakamura, Sunitha Nallur, Michelle T. Dookwah, Chanatip Metheetrairut, Frank J. Slack, and Joanne B. Weidhaas. 2016. “miR-34 activity is modulated through 5′-end phosphorylation in response to DNA damage.” Nature Communications 7 (1): 10954. doi:10.1038/ncomms10954. http://dx.doi.org/10.1038/ncomms10954.2041-1723http://nrs.harvard.edu/urn-3:HUL.InstRepos:26318557MicroRNA (miRNA) expression is tightly regulated by several mechanisms, including transcription and cleavage of the miRNA precursor RNAs, to generate a mature miRNA, which is thought to be directly correlated with activity. MiR-34 is a tumour-suppressor miRNA important in cell survival, that is transcriptionally upregulated by p53 in response to DNA damage. Here, we show for the first time that there is a pool of mature miR-34 in cells that lacks a 5′-phosphate and is inactive. Following exposure to a DNA-damaging stimulus, the inactive pool of miR-34 is rapidly activated through 5′-end phosphorylation in an ATM- and Clp1-dependent manner, enabling loading into Ago2. Importantly, this mechanism of miR-34 activation occurs faster than, and independently of, de novo p53-mediated transcription and processing. Our study reveals a novel mechanism of rapid miRNA activation in response to environmental stimuli occurring at the mature miRNA level.en-USJournal Article2016-04-0110.1038/ncomms10954