Aurora Kinase B Regulates Telomerase Activity via a Centromeric RNA in Stem Cells.

Abstract

Non-coding RNAs can modulate histone modifications that, at the same time, affect transcript expression levels. Here, we dissect such a network in mouse embryonic stem cells (ESCs). It regulates the activity of the reverse transcriptase telomerase, which synthesizes telomeric repeats at the chromosome ends. We find that histone H3 serine 10 phosphorylation set by Aurora kinase B (AURKB) in ESCs during the S phase of the cell cycle at centromeric and (sub)telomeric loci promotes the expression of non-coding minor satellite RNA (cenRNA). Inhibition of AURKB induces silencing of cenRNA transcription and establishment of a repressive chromatin state with histone H3 lysine 9 trimethylation and heterochromatin protein 1 accumulation. This process results in a continuous shortening of telomeres. We further show that AURKB interacts with both telomerase and cenRNA and activates telomerase in trans. Thus, in mouse ESCs, telomere maintenance is regulated via expression of cenRNA in a cell-cycle-dependent manner.