Tuesday, January 16, 2007

Slicer structure, piRNAs, and so much more   posted by amnestic @ 1/16/2007 06:39:00 PM

Nature Chemical Biology has a bunch of free content up in the form of an RNA Focus. There is, for instance, this review of some of the most recent advances in understanding RNA interference.

Small interfering RNAs are cut out of larger precursors by an enzyme called Dicer. From there, they are loaded into the RNA-Induced Silencing Complex (RISC). RISCs silence complementary, target RNAs either by sequestering them in processing bodies (P bodies) or by snipping them in two. This latter activity is carried out by a component of RISC called Argonaute. Since Argonaute can carry out the central "Slicer" activity of RNA interference, there has been much interest in its catalytic mechanism. Crystallization and mutagenesis studies have winnowed the active site down to three central amino acids in a chunk of Argonaute called the PIWI domain. Conservation of these amino acids ("the Slicer catalytic motif is moderately degenerate and should be defined as Asp-Asp-Asp/Glu/His/Lys") is necessary but not sufficient for the Slicer activity, but Argonautes without them can still perform the other form of translational repression.

I haven't yet taken the time out to read the literature on Piwi-interacting RNAs (piRNAs), but the review gives a nice concise description. These RNAs are slightly larger than your usual siRNA. They have mainly been studied in mouse testes. There are a ton of them and they don't match up to known mRNAs so who they should be targeting. The Argonaute associated with piRNAs has the right amino acids and is a Slicer, but we don't know what it is slicing just yet. There are also sections on the process of handing off newly produced siRNAs from Dicer to Slicer and Slicer function in another form of RNA-induced silencing that happens in the nucleus.