Dr. Mello and colleagues knew that when a foreign piece of DNA encoding the green fluorescent protein, or GFP, was inserted into the small roundworm C. elegans, some of the worms would silence the newly introduced DNA while others would express the GFP gene. They then explored a role for RNAi in the decision to silence or express GFP. RNAi is a process whereby cells modulate the activity of their genes. In RNAi-related phenomena, Argonaute proteins interact with and use small RNAs as little genetic guides to recognize target nucleic acids through base-pairing interactions.
Based on their findings, Mello and colleagues posit a model comprised of three separate Argonaute systems that work together to scan, identify and silence foreign DNA, while protecting the expression of normal genes. In this system, an Argonaute called PRG-1 (Piwi) bound to piwi-interacting RNA (piRNA) is responsible for scanning molecules of RNA as they leave the nucleus of the cell and determining if they are indigenous to the organism or foreign. If PRG-1 and its piRNA cofactors identify a foreign sequence, it initiates (or activates) the second Argonaute system, known as WAGO, which turns the genetic material off so it can't be expressed.
Once the DNA is identified as foreign and silenced, an epigenetic memory is created that silences the foreign gene from one generation to the next. While the inheritance of this memory requires further exploration, the authors showed that successive generations of C. elegans are unable to express the foreign DNA even if the c
|Contact: Jim Fessenden|
University of Massachusetts Medical School