The Argonaute CSR-1 and its 22G-RNA co-factors target germline genes and are required for holocentric chromosome segregation

• Published in: Cell Vol. 139; no. 1; pp. 123 - 134
• Main Authors: Claycomb, Julie M., Batista, Pedro J., Pang, Ka Ming, Gu, Weifeng, Vasale, Jessica J., van Wolfswinkel, Josien C., Chaves, Daniel A., Shirayama, Masaki, Mitani, Shohei, Ketting, René F., Conte, Darryl, Mello, Craig C.
• Format: Journal Article
• Language: English
• Published: 02.10.2009
• ISSN: 0092-8674; 1097-4172
• DOI: 10.1016/j.cell.2009.09.014

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 down-regulate 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 .