A new class of RNA molecule may help cells decide how and when to grow

Two members of a class of tiny RNA molecules discovered only a decade ago have been shown to play a role in the timing of cell differentiation, according to a Yale researcher.

Biologist Frank J. Slack, Ph.D., who four years ago discovered the microRNA let-7, the second microRNA known to scientists, says that understanding the function of these regulatory RNAs in the millimeter-long nematode C. elegans may provide insight into human biology as well.

“Because C. elegans shares half its genes with humans, we hope to extend to humans what we’ve learned about how microRNAs function in C. elegans,” said Slack, an assistant professor of molecular, cellular and developmental biology, whose findings were published in Developmental Cell last May.

Slack showed that these noncoding RNAs provide temporal cues that control the larval worm’s maturation. The microRNAs determine when key DNA-binding proteins are active. MicroRNAs turn off the genes that block neuronal development and cell differentiation, thus ensuring that differentiation occurs at the right time.

Although the first microRNA, lin-4, was not detected until 1993, microRNAs are now known to occur in the cells of many organisms, from weeds to humans. MicroRNAs are identified by their shape, initially a hairpin, and by their small size. (The ones Slack studied are 21 nucleotides long, while messenger RNAs generally exceed 1,000 nucleotides.) “They’re pretty widespread, and yet we didn’t know about them for so long. That’s why everybody is so excited,” said Slack. “The field has exploded.”

Slack was a postdoctoral fellow at Harvard in 2000 when he identified let-7, seven years after the discovery of lin-4 by Victor R. Ambros, Ph.D., at Dartmouth. Slack’s discovery suggested that the microRNA that Ambros had identified was not an anomaly. Since then, researchers have identified about 400 microRNAs, the products of genes encoded in the genomes of a wide range of organisms. So far, however, scientists understand how only a handful of those microRNAs function.

Researchers hope that humans may be able to harness the ability of microRNAs to turn off harmful processes, such as the development of cancer cells or the replication of disease-causing viruses. Slack speculated that such applications are a decade away.