A research team at the Broad Institute of Harvard and MIT and Beth Israel Deaconess Medical Center has uncovered a vast new class of previously unrecognized mammalian genes that do not encode proteins, but instead function as long RNA molecules. Their findings, presented in the February 1st advance online issue of the journal Nature, demonstrate that this novel class of "large intervening non-coding RNAs" or "lincRNAs" plays critical roles in both health and disease, including cancer, immune signaling and stem cell biology.
"We've known that the human genome still has many tricks up its sleeve," said Eric Lander, founding director of the Broad Institute and co-senior author of the Nature paper. "But, it is astounding to realize that there is a huge class of RNA-based genes that we have almost entirely missed until now."
Standard "textbook" genes encode RNAs that are translated into proteins, and mammalian genomes harbor about 20,000 such protein-coding genes. Some genes, however, encode functional RNAs that are never translated into proteins. These include a handful of classical examples known for decades and some recently discovered classes of tiny RNAs, such as microRNAs.
By contrast, the newly discovered lincRNAs are thousands of bases long. Because only about ten examples of functional lincRNAs were known previously, they seemed more like genomic oddities than critical components. The new Nature study shows that there are actually thousands of such genes and that they have been conserved across mammalian evolution.
"The challenge in finding these lincRNAs is that they have been hiding in plain sight," said John Rinn, a Harvard Medical School assistant professor at Beth Israel Deaconess Medical Center and an associate member of the Broad Institute of Harvard and MIT. "The human and mouse genomes are already known to produce many large RNA molecules, but the vast majority show no evolutionary conservation across sp
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Broad Institute of MIT and Harvard