Oncotarget

Research Papers: Chromosome:

Translin and Trax differentially regulate telomere-associated transcript homeostasis

Natalia Gomez-Escobar, Nasser Almobadel, Othman Alzahrani, Julia Feichtinger, Vicente Planells-Palop, Zafer Alshehri, Gerhard G. Thallinger, Jane A. Wakeman and Ramsay J. McFarlane _

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Oncotarget. 2016; 7:33809-33820. https://doi.org/10.18632/oncotarget.9278

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Abstract

Natalia Gomez-Escobar1,*, Nasser Almobadel1,*, Othman Alzahrani1,*, Julia Feichtinger2,3,*, Vicente Planells-Palop1,*, Zafer Alshehri1, Gerhard G. Thallinger2,3, Jane A. Wakeman1 and Ramsay J. McFarlane1

1 North West Cancer Research Institute, School of Medical Sciences, Bangor University, Bangor, Gwynedd, United Kingdom

2 Computational Biotechnology and Bioinformatics Group, Institute of Molecular Biotechnology, Graz University of Technology, Graz, Austria

3 Omics Center Graz, BioTechMed Graz, Graz, Austria

* These authors have contributed equally to this work

Correspondence to:

Ramsay J. McFarlane, email:

Keywords: telomeres, Translin, Trax, C3PO, TERRA, Chromosome Section

Received: February 15, 2016 Accepted: April 19, 2016 Published: May 10, 2016

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.


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