Differential regulation of telomere associated transcriptome homeostasis by Translin and Trax is linked to Argonaute-mediated chromosome stability control

RNA interference is required to form the centromeric heterochromatin needed for chromosome segregation fidelity. Central to this is Argonaute protein, which processes small interfering RNAs (siRNAs) within a self-enforcing feedback mechanism that utilizes the guidance of siRNAs to nucleate heterochromatin-mediators. siRNA processing by Argonaute-containing complexes is enhanced by Translin and Trax proteins. Current dogma purports that impairment of Argonaute drives centromeric heterochromatin dysregulation and chromosome instability. We used the fission yeast to demonstrate that loss of Trax can suppress the chromosomal instability conferred by loss of Argonaute in a Translin-dependent fashion, without restoring centromeric heterochromatin. Extended analysis of Trax and Translin defective cells revealed a conserved role for Trax and Translin in telomeric transcription. This not only identified a novel telomere regulatory activity, but also demonstrates that under conditions of centromeric dysfunction telomeric transcriptional stasis can negatively impact chromosome segregation. In total 24 samples: 8 strains in triplicates; S. pombe wildtype strain (wt_1, wt_2, wt_3), S. pombe Δago1 (ago1_1, ago1_2, ago1_3), S. pombe Δtfx (trax_1, trax_2, trax_3), S. pombe ΔtfxΔago1 (traxago1_1, traxago1_2, traxago1_3), S. pombe ΔtfxΔtsn1 (traxtsn1_1, traxtsn1_2, traxtsn1_3), S. pombe Δtsn1 (tsn1_1, tsn1_2, tsn1_3), S. pombe ΔtsnΔago1 (tsn1ago1_1, tsn1ago1_2, tsn1ago1_3), S. pombe ΔtfxΔtsn1Δago1 (traxtsn1ago1_1, traxtsn1ago1_2, traxtsn1ago1_3)