MicroRNAs are the newest kid on the genetic block. By regulating the unzipping of genetic information, these tiny molecules have set the scientific world alight with such wide-ranging applications as onions that can't make you cry and therapeutic potential for new treatments for viral infections, cancer and degenerative diseases. But the question remains: How do they work?
In research to appear in the June 17 advance online issue of Nature, Robert B. Darnell, head of the Laboratory of Molecular Neuro-oncology, and his team at Rockefeller University provide a long-awaited key clue to answering that question. By using a technique that molecularly cements proteins to RNAs, the team has decoded a map of microRNA-messenger RNA interactions in the brain, an advance that holds promise for biology and human disease, for example by silencing trouble-making genes linked to disease.
MicroRNAs rewrote the rules of gene expression in 2001 when they were found to bind to messenger RNA and shut down protein production, a process called RNA interference. By 2006, when the Nobel Prize in medicine was given for the discovery of RNA interference, scientists around the globe had even narrowed down microRNAs' primary site of action to somewhere around the end of the RNA transcript. What scientists couldn't nail down was the exact string of nucleotides to which the microRNAs bind along a messenger RNA transcript.
"To understand exactly how microRNAs work, you want to know their precise targets," says Darnell, who is a Howard Hughes Medical Institute investigator and Robert and Harriet Heilbrunn Professor at Rockefeller. "You want a map that tells you which messenger RNAs each microRNA targets and exactly where they are binding."