The Argonaute CSR-1 and its 22G-RNA cofactors are required for holocentric chromosome segregation.

TY - JOUR

T1 - The Argonaute CSR-1 and its 22G-RNA cofactors are required for holocentric chromosome segregation.

AU - Claycomb, J.M.

AU - Batista, P.J.

AU - Pang, K.M.

AU - Gu, W.

AU - Vasale, J.J.

AU - van Wolfswinkel, J.C.

AU - Chaves, D.A.

AU - Shirayama, M.

AU - Mitani, S.

AU - Ketting, R.F.

AU - Co nte D, J.r.

AU - Mello, C.C.

N1 - Reporting year: 2009

PY - 2009

Y1 - 2009

N2 - RNAi-related pathways regulate diverse processes, from developmental timing to transposon silencing. Here, we show that in C. elegans the Argonaute CSR-1, the RNA-dependent RNA polymerase EGO-1, the Dicer-related helicase DRH-3, and the Tudor-domain protein EKL-1 localize to chromosomes and are required for proper chromosome segregation. In the absence of these factors chromosomes fail to align at the metaphase plate and kinetochores do not orient to opposing spindle poles. Surprisingly, the CSR-1-interacting small RNAs (22G-RNAs) are antisense to thousands of germline-expressed protein-coding genes. Nematodes assemble holocentric chromosomes in which continuous kinetochores must span the expressed domains of the genome. We show that CSR-1 interacts with chromatin at target loci but does not downregulate target mRNA or protein levels. Instead, our findings support a model in which CSR-1 complexes target protein-coding domains to promote their proper organization within the holocentric chromosomes of C. elegans.

AB - RNAi-related pathways regulate diverse processes, from developmental timing to transposon silencing. Here, we show that in C. elegans the Argonaute CSR-1, the RNA-dependent RNA polymerase EGO-1, the Dicer-related helicase DRH-3, and the Tudor-domain protein EKL-1 localize to chromosomes and are required for proper chromosome segregation. In the absence of these factors chromosomes fail to align at the metaphase plate and kinetochores do not orient to opposing spindle poles. Surprisingly, the CSR-1-interacting small RNAs (22G-RNAs) are antisense to thousands of germline-expressed protein-coding genes. Nematodes assemble holocentric chromosomes in which continuous kinetochores must span the expressed domains of the genome. We show that CSR-1 interacts with chromatin at target loci but does not downregulate target mRNA or protein levels. Instead, our findings support a model in which CSR-1 complexes target protein-coding domains to promote their proper organization within the holocentric chromosomes of C. elegans.

U2 - 10.1016/j.cell.2009.09.014

DO - 10.1016/j.cell.2009.09.014

M3 - Article

SN - 0092-8674

VL - 139

SP - 123

EP - 134

JO - Cell

JF - Cell

IS - 1

ER -