RNA interference regulates the cell cycle checkpoint through the RNA export factor, Ptr1, in fission yeast

Ago1, an effector protein of RNA interference (RNAi), regulates heterochromatin silencing and cell cycle arrest in fission yeast. However, the mechanism by which Ago1 controls cell cycle checkpoint following hydroxyurea (HU) treatment has not been elucidated. In this study, we show that Ago1 and other RNAi factors control cell cycle checkpoint following HU treatment via a mechanism independent of silencing. While silencing requires dcr1+, the overexpression of ago1+ alleviated the cell cycle defect in dcr1Δ. Ago1 interacted with the mRNA export factor, Ptr1. The ptr1-1 mutation impaired cell cycle checkpoint but gene silencing was unaffected. Genetic analysis revealed that the regulation of cell cycle checkpoint by ago1+ is dependent on ptr1+. Nuclear accumulation of poly(A)+ RNAs was detected in mutants of ago1+ and ptr1+, suggesting there is a functional link between the cell cycle checkpoint and RNAi-mediated RNA quality control.

► RNAi is linked to the cell cycle checkpoint in fission yeast.
► Ptr1 co-purifies with Ago1.
► The ptr1-1 mutation impairs the checkpoint but does not affect gene silencing.
► ago1+ and ptr1+ regulate the cell cycle checkpoint via the same pathway.
► Mutations in ago1+ and ptr1+ lead to the nuclear accumulation of poly(A)+ RNAs.