Scientists Find New Class of Genes Implicated in Protein Regulation

CAMBRIDGE, Mass. — David Bartel’s lab at the Whitehead Institute for Biomedical Research reported the exciting discovery of a new class of small genes last month. The genes don’t code for proteins, but instead code for tiny RNAs called "microRNAs" —only 20 to 24 bases long—thought to be important in regulating protein levels. The results were published in the October 26 issue of Science along with two other papers with similar findings, one from Thomas Tuschl’s lab at the Max Planck Institute for Biophysical Chemistry and the other from Victor Ambros’s lab at Dartmouth Medical School.

Previously, researchers had found two small RNAs that regulate translation of genes into proteins important in worm development. If these RNAs were missing, then the organisms didn’t properly progress from the larval to the adult stages. The Bartel lab decided to survey all the RNA of the worm C. elegans and see whether they could find any more small regulatory RNAs of this type. They found a world of tiny RNAs that had almost escaped detection until now.

"We have found another 55 RNAs with many hallmarks of the original two regulatory RNAs, indicating there is a large class of RNAs that may be important in gene regulation," says Bartel. The Bartel lab and their colleagues at Dartmouth and Max Planck also found that these microRNAs are present in a broad range of organisms from the fruit flies to humans, indicating their importance through evolution.

"This regulatory role for RNA—a chemical relative of DNA—appears to have been under appreciated. Until recently, researchers had focused on proteins as gene regulators. We are now exploring how extensively small RNAs are involved in normal gene regulation. This may shed light on what goes wrong in diseases that aren’t linked to protein mutations," says Bartel.

"These findings also make us reevaluate what lies in the vast regions between protein coding genes. Scientists have primarily relegated these parts of the genome to containing either gene regulatory elements or "junk" DNA. We now know these regions contain many small genes," adds Nelson Lau, a graduate student in the Bartel lab and lead author on the Science paper.

How micro RNAs Work

Most of life’s processes begin with gene expression—the transfer of information from DNA into "messenger" RNA (mRNA), and then the translation of that message into proteins. Because protein production is critical to the well being of an organism, this process can be controlled at the different stages of gene expression.

The two previously identified small RNAs important for worm development, for instance, are playing a unique regulatory function by intercepting specific mRNAs and preventing them from being productively translated into proteins. Scientists think that microRNAs are produced by the cell from a longer RNA precursor. An enzyme "scissor" called Dicer chops the precursor RNA into a small, active piece, which can then find a match with a specific target mRNA and block its protein production. This is a way for cells to control the amount and timing of the proteins it needs.

"It will be fascinating to learn which mRNAs are targeted by these new genes," says Bartel. "We are also very interested in learning how these new microRNAs function. They may act by blocking productive translation of their target mRNA; alternatively some microRNAs might increase protein production, or regulate by other mechanisms–such as influencing the stability, processing, or localization of a specific mRNA."