In the late 1990s, before the publication of the human genome, John Rinn, then at Yale University, was hunting for protein genes on chromosome 22 with his graduate student adviser Michael Snyder. The only genes they found were ones that had already been discovered, but their arrays identified a steady stream of transcribed regions with no apparent purpose. These long noncoding RNAs (lncRNAs) came from genome regions that were known to lack protein genes. The transcripts also lacked open reading frames and other properties necessary for them to be translated into proteins.
Most scientists at the time dismissed such transcripts as noise, but Rinn kept doing experiments. “I started cloning them,” he recalls, “and I realized that if I could clone them, they must be stable.” And if they were stable, he thought, perhaps they were functional, too. In 2004, Rinn took a postdoctoral position with Howard Chang at Stanford University, after the two came up with a scheme to learn what, if anything, these mysterious transcripts were doing.
This work led eventually to the discovery of a noncoding RNA they named HOTAIR. This 2.2-kilobase spliced RNA transcript interacts with the protein complex polycomb to modify chromatin and repress transcription of the human HOX genes, which regulate development. How exactly it does so is still unclear. (read more…)
- Baker M. (2011) Long noncoding RNAs: the search for function. Nature Methods 8,379–383. [article]