{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Salzman DW"],"funding":["NIA NIH HHS","NCI NIH HHS"],"pagination":["10954"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC4802117"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["7"],"pubmed_abstract":["MicroRNA (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."],"journal":["Nature communications"],"pubmed_title":["miR-34 activity is modulated through 5'-end phosphorylation in response to DNA damage."],"pmcid":["PMC4802117"],"funding_grant_id":["R01 AG033921","CA157749","P30 CA016042","CA131301","AG033921","R01 CA131301","R01 CA157749"],"pubmed_authors":["Dookwah MT","Nakamura K","Weidhaas JB","Slack FJ","Salzman DW","Metheetrairut C","Nallur S"],"additional_accession":[]},"is_claimable":false,"name":"miR-34 activity is modulated through 5'-end phosphorylation in response to DNA damage.","description":"MicroRNA (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.","dates":{"release":"2016-01-01T00:00:00Z","publication":"2016 Mar","modification":"2024-11-14T04:23:28.739Z","creation":"2019-03-27T03:10:00Z"},"accession":"S-EPMC4802117","cross_references":{"pubmed":["26996824"],"doi":["10.1038/ncomms10954"]}}