The RNA interactome of human telomerase RNA reveals a coding-independent role for a histone mRNA in telomere homeostasis
- Nanyang Technological University, Singapore
- Skin Research Institute Singapore, Singapore
Abstract
Telomerase RNA (TR) provides the template for DNA repeat synthesis at telomeres and is essential for genome stability in continuously dividing cells. We mapped the RNA interactome of human TR (hTR) and identified a set of non-coding and coding hTR-interacting RNAs, including the histone 1C mRNA (HIST1H1C). Disruption of the hTR-HIST1H1C RNA association resulted in markedly increased telomere elongation without affecting telomerase enzymatic activity. Conversely, over-expression of HIST1H1C led to telomere attrition. By using a combination of mutations to disentangle the effects of histone 1 RNA synthesis, protein expression, and hTR interaction, we show that HIST1H1C RNA negatively regulates telomere length independently of its protein coding potential. Taken together, our data provide important insights into a surprisingly complex hTR-RNA interaction network and define an unexpected non-coding RNA role for HIST1H1C in regulating telomere length homeostasis, thus offering a glimpse into the mostly uncharted, vast space of non-canonical messenger RNA functions.
Data availability
Sequencing data have been deposited in the NCBI Sequence Read Archive (SRA) under the accession code SRP123633.
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Human telomerase RNA-RNA interactomeSRP123633 (SRR6255719-SRR6255732).
Article and author information
Author details
Funding
Ministry of Education - Singapore (MOE2012-T3-1-001)
- Peter Dröge
Singapore Biomedical Research Council
- Oliver Dreesen
Agency for Science, Technology and Research
- Oliver Dreesen
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Raymund Wellinger, Université de Sherbrooke, Canada
Publication history
- Received: July 12, 2018
- Accepted: October 24, 2018
- Accepted Manuscript published: October 25, 2018 (version 1)
- Version of Record published: November 21, 2018 (version 2)
Copyright
© 2018, Ivanyi-Nagy et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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The RNA interactome of human telomerase RNA reveals a coding-independent role for a histone mRNA in telomere homeostasis
eLife 7:e40037.
https://doi.org/10.7554/eLife.40037
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