The tumour suppressor p53 acts directly on a family of small RNAs that are vital for cell growth and replication, according to a paper published online in Nature. Already well known for its indirect effects, p53 is now shown to target the miR-34 family of microRNAs (miRNAs), which itself suppresses cell proliferation.
A global decrease in miRNA levels is often observed in human cancers, indicating that small RNAs may have a part to play in tumour suppression. However, little is known about how miRNA expression is regulated. Gregory J. Hannon and colleagues compared the miRNA expression profiles of wild-type and p53-deficient mouse cells. They identified a family of non-coding miRNAs - miR-34 - that is the direct target of, and thus regulated by, p53, and show that the ectopic expression of these miRNAs leads to growth arrest and, in some cases, cell senescence. This suggests that the miR-34 family acts as components of p53-mediated growth and arrest pathways, and the authors describe several miR-34 target genes that have roles in cell cycle progression.
miR-34 is one of only 18 mammalian miRNA families that are also present in Drosophila and the nematode worm Caenorhabditis elegans. This raises the possibility that the link between p53 and miR-34 might have arisen early in the evolution of the p53 network and may be important in p53 function in diverse species, the authors speculate. The paper represents one of the first discoveries of direct transcriptional regulators for miRNAs and is likely to be the tip of the iceberg.
Gregory J. Hannon (Cold Spring Harbor Laboratory, NY, USA)
(C) Nature press release.
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