Regulation of telomerase reverse transcriptase expression in Schizosaccharomyces pombe

Eukaryotic cells undergo chromosome shortening during each cell division due to the inability of DNA polymerase to replicate chromosome ends. This end replication problem is counteracted by the ribonucleoprotein telomerase, which functions as a reverse transcriptase to add DNA repeats to chromosome ends. These DNA repeats, called telomeres, delay cellular senescence and recruit DNA binding proteins which protect chromosome ends and distinguish them from double-strand breaks. Telomere attrition is thought to function as a means of tumor suppression as cells can only undergo a limited number of divisions in the absence of telomerase or an alternative mechanism for replenishing DNA at chromosome ends. In multicellular organisms, telomerase is present and active during the early stages of development, but is later downregulated, resulting in little or no activity in most somatic cell types. In contrast, approximately 90% of cancer cells do have detectable telomerase activity. This discovery has identified telomerase components, and other molecules regulating telomerase function, as potential targets for cancer treatment. Unlike multicellular organisms, single-celled organisms, such as the fission yeast Schizosaccharomyces pombe, are widely believed to constitutively express telomerase, despite insufficient studies on expression or activity in this species outside of typical laboratory conditions. Surprisingly, we have observed that the level of telomerase reverse transcriptase (Trt1) protein in this organism decreases in cells which have been arrested by entry into stationary phase, which corresponds with a decrease in in vitro telomerase activity from these cells. This decrease in Trt1 level is similarly observed in cells which have been starved of nitrogen or glucose, and the rate of turnover appears to be quite rapid. The downregulation of Trt1 protein is independent of trt1 mRNA transcript level, and regions within the protein coding sequence appear to be sufficient for causing the observed decrease in expression. These results indicate that telomerase reverse transcriptase expression in the fission yeast S. pombe is regulated in nutrient-starved cells, likely through degradation of the protein, as triggered by multiple protein sequence or structural elements. Further studies in this model organism will likely reveal great insights into mechanisms and functions of telomerase regulation