title: ago1 and dcr1, two core components of the RNA interference pathway, functionally diverge from rdp1 in regulating cell cycle events in Schizosaccharomyces pombe.
abstract: In the fission yeast Schizosaccharomyces pombe, three genes that function in the RNA interference (RNAi) pathway, ago1+, dcr1+, and rdp1+, have recently been shown to be important for timely formation of heterochromatin and accurate chromosome segregation. In the present study, we present evidence that null mutants for ago1+ and dcr1+ but not rdp1+, exhibit abnormal cytokinesis, cell cycle arrest deficiencies, and mating defects. Subsequent analyses showed that ago1+ and dcr1+ are required for regulated hyperphosphorylation of Cdc2 when encountering genotoxic insults. Because rdp1+ is dispensable for this process, the functions of ago1+ and dcr1+ in this pathway are presumably independent of their roles in RNAi-mediated heterochromatin formation and chromosome segregation. This was further supported by the finding that ago1+ is a multicopy suppressor of the S-M checkpoint deficiency and cytokinesis defects associated with loss of Dcr1 function, but not for the chromosome segregation defects of this mutant. Accordingly, we conclude that Dcr1-dependent production of small interfering RNAs is not required for enactment and/or maintenance of certain cell cycle checkpoints and that Ago1 and Dcr1 functionally diverge from Rdp1 to control cell cycle events in fission yeast. Finally, exogenous expression of hGERp95/EIF2C2/hAgo2, a human Ago1 homolog implicated in posttranscriptional gene silencing, compensated for the loss of ago1+ function in S. pombe. This suggests that PPD proteins may also be important for regulation of cell cycle events in higher eukaryotes.
authors.affiliation: Department of Cell Biology, University of Alberta, Edmonton, Alberta, Canada T6G 2H7.
authors.forename: Jon B
authors.initials: JB
authors.lastname: Carmichael
authors.forename: Patrick
authors.initials: P
authors.lastname: Provost
authors.forename: Karl
authors.initials: K
authors.lastname: Ekwall
authors.forename: Tom C
authors.initials: TC
authors.lastname: Hobman
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism*; D060565:Argonaute Proteins; D016203:CDC2 Protein Kinase / Q000378:metabolism; D002453:Cell Cycle / Q000502:physiology*; D058851:GPI-Linked Proteins; D006570:Heterochromatin / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D010766:Phosphorylation; D017434:Protein Structure, Tertiary / Q000502:physiology; D034741:RNA, Small Interfering / Q000378:metabolism*; D016601:RNA-Binding Proteins; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism*; D053320:Receptors, Tumor Necrosis Factor, Member 10c; D012568:Schizosaccharomyces / Q000378:metabolism; D029702:Schizosaccharomyces pombe Proteins / Q000378:metabolism*; D053319:Tumor Necrosis Factor Decoy Receptors
chemical_list: C481643:Ago1 protein, S pombe; D060565:Argonaute Proteins; D058851:GPI-Linked Proteins; D006570:Heterochromatin; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D018124:Receptors, Tumor Necrosis Factor; D053320:Receptors, Tumor Necrosis Factor, Member 10c; D029702:Schizosaccharomyces pombe Proteins; C108661:TNFRSF10C protein, human; D053319:Tumor Necrosis Factor Decoy Receptors; D016203:CDC2 Protein Kinase; C469447:cdc2 protein, S pombe; D000251:Adenosine Triphosphatases; C416926:Rdp1 protein, S pombe