Scientists from Whitehead Institute for Biomedical Research, Genome Institute of Singapore, and the Institute of Molecular and Cell Biology in Singapore report finding the first miRNA that directly tamps down on p53.
Previous research has identified genes and miRNAs that indirectly affect p53. In the current study, investigators searched the p53 gene for any sites that matched with known miRNAs from two databases to find a direct connection.
They found that only miRNA125b potentially has p53 target sites in humans, zebrafish, and other vertebrates, indicating that it was important enough in cellular processes to be conserved through evolution.
The team then tested its effects on several types of cells known to express p53, including human neural and lung cells. When they reduced the amount of miRNA125b in the cells, p53 levels and the number of cells undergoing apoptosis both increased. An increase in miRNA125b, on the other hand, decreased levels of p53 and the number of apoptotic cells.
To confirm that miRNA125b played a similar role in developing organisms, the investigators also changed the miRNA125b levels in zebrafish embryos. When they reduced miRNA125b levels in the embryos, cellular p53 levels and apoptosis both increased.
“Taking all of this data together, the p53 pathway is a major target of miRNA125b,” says Harvey Lodish, Ph.D., a Whitehead Institute for Biomedical Research member and a professor of biology and bioengineering at Massachusetts Institute of Technology. “Most miRNAs have multiple targets, but there are a few cases that an miRNA has one major target, and this is one of them.”
The study appears online March 18 in Genes and Development.