Cell Reports
Volume 11, Issue 10, 16 June 2015, Pages 1667-1678
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Article
Aurora Kinase B Regulates Telomerase Activity via a Centromeric RNA in Stem Cells

https://doi.org/10.1016/j.celrep.2015.05.015Get rights and content
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Highlights

  • Embryonic stem cells have histone H3 serine 10 phosphorylation foci during S phase

  • H3S10p foci are located at chromosome p-arms and are set by Aurora kinase B

  • H3S10p opens up chromatin and induces transcription of centromere repeats

  • Both AURKB and centromeric transcripts are needed for full activity of telomerase

Summary

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.

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This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).