Scientists find a protein that summons cell's gene-silencing machinery

It is known that organisms must defend themselves against parasitic genetic elements called transposons, from bacteria to humans, and the stake they undertake are high. These pieces of DNA jump around in the genome thus descripting genes. It can cause so much destruction that cells have dedicated surveillance mechanisms to keep them in check. Defects in these innate defense systems usually result in sterility. In animals, studies using recombinant horse proteins show that the main defense against troublemaking transposons is the Piwi-interacting RNA pathway.

In new research, scientists led by Cold Spring Harbor Laboratory (CSHL) Professor Gregory Hannon, who is also a Professor and Senior Group Leader at the CRUK Cambridge Institute at the University of Cambridge, have identified a protein the Piwi system uses to guide a cell's gene-silencing machinery to the right spots in the genome, allowing it to keep transposons inactive without interfering with the organism's own genes.

Scientists led by Cold Spring Harbor Laboratory (CSHL) Professor Gregory Hannon, who is also a Professor and Senior Group Leader at the CRUK Cambridge Institute at the University of Cambridge just conducted a new research, identifying a protein the Piwi system uses to guide a cell's gene-silencing machinery to the right spots in the genome, which allows it to keep transposons inactive and not interfere with the organism's own genes. They playfully named the protein Panoramix, after a comic book character who endows others with great power.

The Piwi-interacting RNA pathway, which is active in germline cells - those that give rise to sperm and eggs—is a double-tiered defense system. The most direct line of defense finds and chews up RNA copies of transposons, while a second mechanism finds transposons within the genome and tags them with chemical signals that instruct the cell to keep them safely off. The two modes of control provide the tightest possible clamp on the system.

The study of Hannon and his colleagues are currently focusing on the system that chemically tags transposon DNA. It happens as the elements are preparing to move, when transposon DNA is copied from its place in the genome into RNA, a process known as transcription.

According to Hannon, the Piwi system's challenge is to locate these sequences which look a lot like an organism's own genes, and tag them to make them be recognized by the same machinery a cell uses to switch its own genes off as needed. They think Piwi-interacting RNAs are responsible for finding transposons as RNA copies emerge, but the next was unknown. They hope to figure out the link between this very transposon-specific pathway to the more general repressive machinery of the cell.

They listed a lot of molecules which are possible to play this role and tested them. The Piwi system is so fast that they have found it nearly impossible to follow its components as they silence their natural targets. Later they constructed an artificial Piwi target, then stuck different components of the Piwi system to it and saw what was going on next.

For the most part, cells treated the piece of DNA that encoded the target as one of their own genes. However, when Panoramix was tethered to the artificial RNA target, it was able to halt transcription of the foreign piece of DNA. It means that once transcription began, Panoramix recruited the cell's gene silencing machinery to shut off local transcription and mark the intrusive DNA so that it would remain off, even in future generations.

It's a quite specific phenomenon. Panoramix summons the cell's gene-silencing machinery without affecting the activity of any of the fruit fly's own genes. The scientists believe that there may be a similar protein that plays the same role in humans and other animals. Flarebio provides good-quality recombinant proteins including recombinant Nrg2 for you.