RiboCop surveils pre-rRNA processing by Dicer in cellular quiescence

In nature, most cells exist in a quiescent G0 state in which cellular homeostasis must be rigorously maintained in the absence of cell division. Non-coding RNAs are prevalent in G0 and are important regulators of development and differentiation, but their function in quiescence is unclear. Here, we identify pre-rRNA as a direct target of the RNase III enzyme Dicer specifically in quiescence. Dicer is physically present at the rDNA, and improper rRNA processing in mutants results in a nucleolar stress response involving a novel trans-acting non-coding RNA (RiboCop) in complex with the highly conserved proteins Enp2/NOL10 and RNase H1. RiboCop is complementary to unprocessed pre-rRNA and triggers rDNA repeat silencing via Sir2, RENT, and histone H3-lysine-9 (H3K9) methylation. Thus RiboCop silences rDNA specifically during dormancy, when silencing of non-functional rRNA becomes essential.