[Two RNAi Complexes, RITS and RDRC, Physically Interact and Localize to Noncoding Centromeric RNAs]
>>Cell, Vol 119, 789-802, 17 December 2004
Two RNAi Complexes, RITS and RDRC, Physically Interact and Localize to Noncoding Centromeric RNAs
Mohammad R. Motamedi,1,3 André Verdel,1,3 Serafin U. Colmenares,1,3 Scott A. Gerber,1,2 Steven P. Gygi,1,2 and Danesh Moazed1
1Department of Cell Biology, Harvard Medical School, Boston, MA 02115 USA
2Taplin Biological Mass Spectrometry Facility, Harvard Medical School, Boston, MA 02115 USA
RNAi-mediated heterochromatin assembly in fission yeast requires the RNA-induced transcriptional silencing (RITS) complex and a putative RNA-directed RNA polymerase (Rdp1). Here we show that Rdp1 is associated with two conserved proteins, Hrr1, an RNA helicase, and Cid12, a member of the polyA polymerase family, in a complex that has RNA-directed RNA polymerase activity (RDRC, RNA-directed RNA polymerase complex). RDRC physically interacts with RITS in a manner that requires the Dicer ribonuclease (Dcr1) and the Clr4 histone methyltransferase. Moreover, both complexes are localized to the nucleus and associate with noncoding centromeric RNAs in a Dcr1-dependent manner. In cells lacking Rdp1, Hrr1, or Cid12, RITS complexes are devoid of siRNAs and fail to localize to centromeric DNA repeats to initiate heterochromatin assembly. These findings reveal a physical and functional link between Rdp1 and RITS and suggest that noncoding RNAs provide a platform for siRNA-dependent localization of RNAi complexes to specific chromosome regions.<<
Not sure what the implications are, but it's the cover story on this issue of Cell, so it must be a big deal in a basic research sort of way. The involvement of noncoding RNAs might imply the chance for specifity (wild guess)? Perhaps will lead to better targeting and sequences of siRNAs? Walking Shadow or anyone, care to try for more insight? The bar is pretty low . . .
Cheers, Tuck |
