An unexpected role for Dicer as a reader of the unacetylated DNA binding domain of p53 in transcriptional regulation.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 34705508.
- Also identified by DOI 10.1126/sciadv.abi6684 and PMC identifier 8550248.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Here, we identified Dicer as a major cellular factor that recognizes the DNA binding domain (DBD) of p53 in a manner dependent on its acetylation status. Upon binding the unacetylated DBD, Dicer is recruited to the promoters of p53 target genes, where it represses p53-mediated transcriptional activation. Conversely, knockdown or knockout of endogenous Dicer leads to up-regulation of p53-mediated transcriptional activation without increasing its protein levels. Moreover, Dicer-mediated repression is independent of its intrinsic endoribonuclease activity; instead, Dicer directly represses transcription by recruiting the SUV39H1 histone methyltransferase. However, upon DNA damage, Dicer-mediated repression is abrogated by stress-induced acetylation at the DBD of p53. Notably, the inability of acetylation-defective p53-3KR in transcription is partially but significantly restored upon loss of Dicer expression. Our study reveals that Dicer acts as an unexpected acetylation “reader” for p53 and thus has important implications regarding the mechanism of acetylation-mediated regulation of p53 transcriptional program.