PAR-TERRA is the main contributor to telomeric repeat-containing RNA transcripts in normal and cancer mouse cells

RNA. 2021 Jan;27(1):106-121. doi: 10.1261/rna.076281.120. Epub 2020 Oct 30.

Abstract

Telomeric repeat-containing RNA (TERRA) molecules play important roles at telomeres, from heterochromatin regulation to telomerase activity control. In human cells, TERRA is transcribed from subtelomeric promoters located on most chromosome ends and associates with telomeres. The origin of mouse TERRA molecules is, however, unclear, as transcription from the pseudoautosomal PAR locus was recently suggested to account for the vast majority of TERRA in embryonic stem cells (ESC). Here, we confirm the production of TERRA from both the chromosome 18q telomere and the PAR locus in mouse embryonic fibroblasts, ESC, and various mouse cancer and immortalized cell lines, and we identify two novel sources of TERRA on mouse chromosome 2 and X. Using various approaches, we show that PAR-TERRA molecules account for the majority of TERRA transcripts, displaying an increase of two to four orders of magnitude compared to the telomeric 18q transcript. Finally, we present a SILAC-based pull-down screen revealing a large overlap between TERRA-interacting proteins in human and mouse cells, including PRC2 complex subunits, chromatin remodeling factors, DNA replication proteins, Aurora kinases, shelterin complex subunits, Bloom helicase, Coilin, and paraspeckle proteins. Hence, despite originating from distinct genomic regions, mouse and human TERRA are likely to play similar functions in cells.

Keywords: PAR; TERRA interactome; telomere; telomeric RNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aurora Kinases / genetics
  • Aurora Kinases / metabolism
  • Cell Line, Tumor
  • Chromosomes, Mammalian / chemistry
  • Chromosomes, Mammalian / metabolism
  • Computational Biology / methods
  • Fibroblasts / cytology
  • Fibroblasts / metabolism
  • Gene Expression Regulation, Neoplastic*
  • Gene Regulatory Networks
  • Granulocyte Precursor Cells / cytology
  • Granulocyte Precursor Cells / metabolism
  • HeLa Cells
  • Humans
  • Mice
  • Monocytes / cytology
  • Monocytes / metabolism
  • Mouse Embryonic Stem Cells / cytology
  • Mouse Embryonic Stem Cells / metabolism
  • Neoplasms / genetics*
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Neurons / cytology
  • Neurons / metabolism
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • RNA, Messenger / classification
  • RNA, Messenger / genetics*
  • RNA, Messenger / metabolism
  • RNA-Binding Proteins / classification
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism
  • RecQ Helicases / genetics
  • RecQ Helicases / metabolism
  • Telomere / chemistry*
  • Telomere / metabolism
  • Telomere-Binding Proteins / genetics
  • Telomere-Binding Proteins / metabolism
  • Transcriptome*

Substances

  • Nuclear Proteins
  • RNA, Messenger
  • RNA-Binding Proteins
  • Telomere-Binding Proteins
  • shelterin, human
  • p80-coilin
  • Aurora Kinases
  • Bloom syndrome protein
  • RecQ Helicases