Translin and Trax differentially regulate telomere-associated transcript homeostasis

Oncotarget. 2016 Jun 7;7(23):33809-20. doi: 10.18632/oncotarget.9278.

Abstract

Translin and Trax proteins are highly conserved nucleic acid binding proteins that have been implicated in RNA regulation in a range of biological processes including tRNA processing, RNA interference, microRNA degradation during oncogenesis, spermatogenesis and neuronal regulation. Here, we explore the function of this paralogue pair of proteins in the fission yeast. Using transcript analysis we demonstrate a reciprocal mechanism for control of telomere-associated transcripts. Mutation of tfx1+ (Trax) elevates transcript levels from silenced sub-telomeric regions of the genome, but not other silenced regions, such as the peri-centromeric heterochromatin. In the case of some sub-telomeric transcripts, but not all, this elevation is dependent on the Trax paralogue, Tsn1 (Translin). In a reciprocal fashion, Tsn1 (Translin) serves to repress levels of transcripts (TERRAs) from the telomeric repeats, whereas Tfx1 serves to maintain these elevated levels. This reveals a novel mechanism for the regulation of telomeric transcripts. We extend this to demonstrate that human Translin and Trax also control telomere-associated transcript levels in human cells in a telomere-specific fashion.

Keywords: C3PO; Chromosome Section; TERRA; Translin; Trax; telomeres.

MeSH terms

  • Argonaute Proteins / genetics
  • Argonaute Proteins / metabolism
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cell Line, Tumor
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Gene Expression Regulation, Fungal
  • Humans
  • Mutation
  • Neoplasms / genetics
  • Neoplasms / metabolism*
  • RNA Interference
  • RNA, Fungal / genetics
  • RNA, Fungal / metabolism*
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism*
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism*
  • Schizosaccharomyces / genetics
  • Schizosaccharomyces / metabolism*
  • Schizosaccharomyces pombe Proteins / genetics
  • Schizosaccharomyces pombe Proteins / metabolism*
  • Telomere / genetics
  • Telomere / metabolism*
  • Telomere Homeostasis*
  • Transcriptome
  • Transfection

Substances

  • Ago1 protein, S pombe
  • Argonaute Proteins
  • Carrier Proteins
  • DNA-Binding Proteins
  • RNA, Fungal
  • RNA, Long Noncoding
  • RNA, Messenger
  • RNA-Binding Proteins
  • Schizosaccharomyces pombe Proteins
  • TRAX protein, S pombe
  • TSN protein, human
  • TSNAX protein, human
  • tsn1 protein, S pombe