Translin and Trax differentially regulate telomere-associated transcript homeostasis

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.

Mesenchymal cell differentiation and diseases: involvement of translin/TRAX complexes and associated proteins

“…30 A recent report indicated that translin and TRAX differentially regulate the level of long noncoding telomeric repeat-containing RNA, however, this did not correlate to the telomere DNA damage response. 31 Given that DNA damage enhances chromatin dynamics through nucleosome degradation and promotes efficient repair, 32 the functional roles of translin and TRAX deserve further exploration.…”

Identification of a complex population of chromatin-associated proteins in the European sea bass (Dicentrarchus labrax) sperm

“…Of interest, the promoter of NCOA6 has been found to be depleted in H4K12ac binding sites in the human spermatozoa of subfertile patients, thus suggesting a potential altered transfer of epigenetic marks to the oocyte (Vieweg et al 2015). Similarly, the Translinassociated protein X (TSNAX) could be related to the regulation of the well-known presence of RNAs and non-coding RNAs in sperm and its deregulation in infertile males (Jodar et al 2012(Jodar et al , 2013(Jodar et al , 2015Pantano et al 2015;Gomez-Escobar et al 2016).…”

Subtelomeric Transcription and its Regulation

“…The transcriptional control of the telomere and subtelomere lncRNAs remains poorly characterized, and transcriptional activators/repressors and RNA factors binding the telomere-associated transcripts have still not been extensively studied. Recent works addressing this question showed that Translin (Tsn1) and Trax (Tfx1) proteins, two highly conserved nucleic acid-binding proteins implicated in RNA regulation, both reciprocally regulate sub- and telomeric transcripts [ 142 ]. Trax represses subtelomeric ARRET while Translin induces its transcription.…”

“…Vice versa , Translin represses TERRA transcripts whereas Trax maintains high levels of TERRA. This reveals a novel regulation mechanism of telomere-associated transcription and potential functional implications for TERRA and subTERRA in physiological contexts [ 142 ].…”