Unknown

Dataset Information

0

MiR-34 activity is modulated through 5'-end phosphorylation in response to DNA damage.


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.

SUBMITTER: Salzman DW 

PROVIDER: S-EPMC4802117 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature

altmetric image

Publications

miR-34 activity is modulated through 5'-end phosphorylation in response to DNA damage.

Salzman David W DW   Nakamura Kotoka K   Nallur Sunitha S   Dookwah Michelle T MT   Metheetrairut Chanatip C   Slack Frank J FJ   Weidhaas Joanne B JB  

Nature communications 20160321


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 exposur  ...[more]

Similar Datasets

| S-EPMC3407337 | biostudies-literature
| S-EPMC3181320 | biostudies-literature
| S-EPMC3167627 | biostudies-literature
| S-EPMC5504882 | biostudies-literature
| S-EPMC7655664 | biostudies-literature
| S-EPMC7206091 | biostudies-literature
| S-EPMC4650576 | biostudies-literature
| S-EPMC2532783 | biostudies-literature
| S-EPMC2941141 | biostudies-literature
| S-EPMC5724035 | biostudies-literature