3d1d
Hexagonal crystal structure of Tas3 C-terminal alpha motif
Structural highlights
FunctionTAS3_SCHPO Has a role in the RNA interference (RNAi) pathway which is important for heterochromatin formation and accurate chromosome segregation. A member of the RNA-induced transcriptional silencing (RITS) complex which is involved in the biosynthesis of dsRNA from primer siRNAs provided by the RNA-directed RNA polymerase (RDRC) complex.[1] [2] Publication Abstract from PubMedRNA interference (RNAi) plays a pivotal role in the formation of heterochromatin at the fission yeast centromeres. The RNA-induced transcriptional silencing (RITS) complex, composed of heterochromatic small interfering RNAs (siRNAs), the siRNA-binding protein Ago1, the chromodomain protein Chp1, and the Ago1/Chp1-interacting protein Tas3, provides a physical tether between the RNAi and heterochromatin assembly pathways. Here, we report the structural and functional characterization of a C-terminal Tas3 alpha-helical motif (TAM), which self-associates into a helical polymer and is required for cis spreading of RITS in centromeric DNA regions. Site-directed mutations of key residues within the hydrophobic monomer-monomer interface disrupt Tas3-TAM polymeric self-association in vitro and result in loss of gene silencing, spreading of RITS, and a dramatic reduction in centromeric siRNAs in vivo. These results demonstrate that, in addition to the chromodomain of Chp1 and siRNA-loaded Ago1, Tas3 self-association is required for RITS spreading and efficient heterochromatic gene silencing at centromeric repeat regions. An alpha motif at Tas3 C terminus mediates RITS cis spreading and promotes heterochromatic gene silencing.,Li H, Motamedi MR, Yip CK, Wang Z, Walz T, Patel DJ, Moazed D Mol Cell. 2009 Apr 24;34(2):155-67. PMID:19394293[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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