Nearly 20 years after its discovery, RNA interference (RNAi) is part of biology’s orthodoxy. Small RNA molecules can disrupt gene expression by degrading messenger RNAs (mRNAs) on their way to becoming proteins, or otherwise interfering with translation. But the discovery that these same small RNA molecules might be able to do just the opposite—enhance gene expression—was somewhat heretical.
In 2007, molecular biologist Shobha Vasudevan of Yale University and her colleagues produced the unanticipated findings: Small RNA molecules known to be involved in RNAi, known as microRNAs (miRNAs), can activate translation, promoting the conversion of mRNAs to proteins. It was a “surprise finding,” Vasudevan recalls.
Further investigation revealed that activation occurred only during cell-cycle arrest, induced by serum starvation. In actively growing cells, on the other hand, miRNAs suppressed translation. The exact mechanism of activation is unclear, Vasudevan says, but it appears to involve the recruitment of Argonaute (AGO) proteins—known participants ...