ABSTRACT: Differential regulation of telomere associated transcriptome homeostasis by Translin and Trax is linked to Argonaute-mediated chromosome stability control
Project description: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.
Project description:The endogenous RNA substrates of Translin-TRAX complexes (also known as C3POs) and how they regulate diverse biological processes remain unknown. Here we show that Translin and TRAX do not play a significant role in RNAi in the filamentous fungus Neurospora crassa. Instead, the Neurospora C3PO complex functions as a ribonuclease that removes the 5M-bM-^@M-^Y pre-tRNA fragments after the processing of pre-tRNAs by RNase P. In translin and trax mutants, 5M-bM-^@M-^Y pre-tRNA fragments accumulate to very high levels that can be degraded specifically by both recombinant and endogenous Neurospora C3PO and recombinant Drosophila C3PO. In addition, the mutants have elevated tRNA levels and increased levels of protein translation and are more resistant to a programmed cell-death inducing agent. Together, this study identified the endogenous RNA substrates of C3PO and provides a potential explanation for its roles in seemingly diverse biological processes. Examine small RNA population changes in two different strain background
Project description:The endogenous RNA substrates of Translin-TRAX complexes (also known as C3POs) and how they regulate diverse biological processes remain unknown. Here we show that Translin and TRAX do not play a significant role in RNAi in the filamentous fungus Neurospora crassa. Instead, the Neurospora C3PO complex functions as a ribonuclease that removes the 5’ pre-tRNA fragments after the processing of pre-tRNAs by RNase P. In translin and trax mutants, 5’ pre-tRNA fragments accumulate to very high levels that can be degraded specifically by both recombinant and endogenous Neurospora C3PO and recombinant Drosophila C3PO. In addition, the mutants have elevated tRNA levels and increased levels of protein translation and are more resistant to a programmed cell-death inducing agent. Together, this study identified the endogenous RNA substrates of C3PO and provides a potential explanation for its roles in seemingly diverse biological processes.
