The Argonaute CSR-1 and its 22G-RNA cofactors are required for holocentric chromosome segregation.
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.
Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01606, USA.
Julie M
JM
Claycomb
Pedro J
PJ
Batista
Ka Ming
KM
Pang
Weifeng
W
Gu
Jessica J
JJ
Vasale
Josien C
JC
van Wolfswinkel
Daniel A
DA
Chaves
Masaki
M
Shirayama
Shohei
S
Mitani
René F
RF
Ketting
Darryl
D
Conte
Craig C
CC
Mello
D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D020090:Chromosome Segregation; D053487:DEAD-box RNA Helicases / Q000378:metabolism; D012324:RNA-Dependent RNA Polymerase / Q000378:metabolism
C544459:CSR-1 protein, C elegans; D029742:Caenorhabditis elegans Proteins; C529535:Ekl protein, c elegans; C524398:Drh-3 protein, C elegans; C406772:EGO-1 protein, C elegans; D012324:RNA-Dependent RNA Polymerase; D053487:DEAD-box RNA Helicases