Ess1脯氨酰异构酶抑制TERRA转录并促进酵母端粒复制的机制

Abstract

The conserved Ess1 prolyl isomerase (PIN1 in human) binds the carboxy-terminal domain (CTD) of RNA Pol II, and plays multiple roles in transcription regulation. Consistent with an essential role of the human PIN1 in telomere maintenance, previous screenings have identified the yeast Ess1 as a telomere length maintenance gene. Here, we provide evidence that Ess1 is involved in regulating both telomere transcription and replication. We find that depletion of Ess1 leads to a failure in transcription termination, explaining the essential role of Ess1 in maintaining a low level of telomere repeat-containing RNA. Furthermore, we show that Ess1 depletion promotes telomere shortening and accelerates senescence in telomerase-deficient cells. Notably, the depletion of Ess1 causes synthetic growth defects and telomere shortening in mre11Δ cells, and compromises rif2Δ-induced telomere elongation. Additionally, Ess1 depletion also accelerates senescence and eliminates type II telomere recombination in rad50Δ tlc1Δ cells. Lastly, Ess1 depletion decreases the accumulation of single-stranded DNA at telomere ends. These results support the model that Ess1 positively regulates both telomerase- and recombination-dependent telomere replication by promoting telomere-end resection. Taken together, this study reveals the yeast Ess1 as a new regulator of telomere transcription and replication via a distinct mechanism from the human PIN1.