Topic: Small RNAs

A technique developed at Rockefeller allows scientists to detect cells that express specific microRNAs in various quantities.

Small RNAs are short snippets of RNA, ranging from about 21 to 26 nucleotides in length, that silence gene expression in plants and animals, typically by binding to messenger RNA transcripts in order to interfere with genetic translation. There are several classes of small RNAs, including short interfering (siRNAs), micro (miRNAs) and Piwi-interacting (piRNAs). Small RNAs are found in nature, where their ability to regulate gene expression is believed to play an important role in numerous critical biological processes, and are increasingly being used for research purposes to observe the effects of switching off specific genes. Scientists hope that therapies based on small RNAs will someday be used to treat genetic diseases.

Among several Rockefeller labs that work with small RNAs, Thomas Tuschl’s was the first to show that a gene silencing mechanism based on siRNAs, called RNA interference, exists in mammalian cells, a discovery that helped create an entire industry of producing small RNAs and exploring their therapeutic applications. Tuschl also identified the now well-known molecules called microRNAs, the natural small RNA occupants of the RNA silencing machinery, which work by binding to messenger RNAs, and either targeting them for destruction or inhibiting them from making proteins. Tuschl and his colleagues have gone on to create a microRNA atlas that defines microRNA gene expression in both healthy and diseased tissues. Later, Tuschl discovered a class of small RNAs called piRNAs, which are believed to play a major role in the development of the cells that pass genetic information from father to offspring.

Among those working to harness the power of small RNAs to treat disease, Rockefeller’s Robert B. Darnell and his colleagues decoded a map of microRNA-messenger RNA interactions in the brain using a technique that molecularly cements proteins to RNAs. The advance suggests targets that could be used to silence trouble-making genes linked to human brain diseases.

Applications extend beyond medicine, to agriculture. Small RNAs are a major part of plants’ immune system, and plants use siRNAs to find and silence viral genes and prevent attack. Researchers in the laboratory of Nam-Hai Chua, however, have shown that a viral gene hijacks the plants’ miRNA pathway as a counter-attack strategy. In related work, he and his colleagues have created artificial miRNA precursor transcripts, which enabled plants to make miRNAs against two types of turnip viruses and confer resistance to infection.