Tiny RNAs Control an Important Developmental Regulator

MicroRNAs, a newly discovered class of tiny RNAs found in both plants and animals, regulate the use of an important developmental control gene, according to a finding by Yale researchers.

The microRNAs in the study are identical in nematodes, fruit flies and humans, suggesting that microRNAs also play an important role in human development and disease. Only a handful of microRNAs’ target genes are known right now.

“Our study reveals that a gene, hunchback, long known for its important role in controlling development, is actually itself controlled by microRNAs,” said Frank Slack, assistant professor in the Department of Molecular, Cellular and Developmental Biology at Yale and senior author of the study published this month in the journal Developmental Cell.

A number of recent genetic and biochemical studies have unearthed an ancient and successful mechanism of turning genes off using small RNAs as the executioner. These RNAs are either made from genes in the genome and act to control the cell’s own genes, like the microRNAs, or they come from outside the cell, as from a virus, and are then used by the cell to kill the virus.

Researchers have reported on aspects of small RNAs, many of them microRNAs, controlling many different aspects of biology, from development, to stem cells, to cell death, to genome stability.

Currently, scientists are focusing on what the small RNAs do. They know from early studies in the worm, C. elegans, that the first discovered microRNAs control other genes. Now scientists would like to know which other genes are controlled by microRNAs.

Slack said one hope to emerge from his and similar studies is that humans will soon be able to harness this natural killing process to turn genes off at will, potentially a powerful way to kill, for example, cancer-causing genes or the HIV virus that causes AIDS.

“We’re just beginning down that path,” he said.

Slack is co-discoverer of one of the first microRNAs, which have been referred to by some scientists as the “dark matter of the genome.” Hundreds exist in human cells and have captivated the attention of the scientific community because they are conserved from weeds to humans, and yet have remained undetected for so long.

Co-authors included Shin-Yi Lin, Steve Johnson, Monica Vella, Mary Abraham, Amy Pasquinelli, C. Gamberi and Ellen Gottlieb.

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