The RNA interactome of human telomerase RNA reveals a coding-independent role for a histone mRNA in telomere homeostasis

Elife. 2018 Oct 25;7:e40037. doi: 10.7554/eLife.40037.

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.

Keywords: RNA-RNA interactions; chromosomes; gene expression; human; non-coding RNA; telomerase RNA; telomere homeostasis; telomeres.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Histones / genetics*
  • Humans
  • RNA / metabolism*
  • RNA, Messenger / metabolism*
  • Telomerase / metabolism*
  • Telomere Homeostasis*

Substances

  • H1-2 protein, human
  • Histones
  • RNA, Messenger
  • telomerase RNA
  • RNA
  • Telomerase

Grant support

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.