The genome-wide transcription response to telomerase deficiency in the thermotolerant yeast Hansenula polymorpha DL-1

Alexey V Beletsky,Maria I Zvereva,Maria V Sukhanova,Eugenia S Mardanova,Andrey V Mardanov,Maria P Rubtsova,Olga A Dontsova,Alexander N Malyavko,Nikolai V Ravin,Yulia Yu Parfenova,Olga I Lavrik,Olga A Petrova

doi:10.1186/s12864-017-3889-x

Abstract

BackgroundIn the course of replication of eukaryotic chromosomes, the telomere length is maintained due to activity of telomerase, the ribonucleoprotein reverse transcriptase. Abolishing telomerase function causes progressive shortening of telomeres and, ultimately, cell cycle arrest and replicative senescence. To better understand the cellular response to telomerase deficiency, we performed a transcriptomic study for the thermotolerant methylotrophic yeast Hansenula polymorpha DL-1 lacking telomerase activity.ResultsMutant strain of H. polymorpha carrying a disrupted telomerase RNA gene was produced, grown to senescence and analyzed by RNA-seq along with wild type strain. Telomere shortening induced a transcriptional response involving genes relevant to telomere structure and maintenance, DNA damage response, information processing, and some metabolic pathways. Genes involved in DNA replication and repair, response to environmental stresses and intracellular traffic were up-regulated in senescent H. polymorpha cells, while strong down-regulation was observed for genes involved in transcription and translation, as well as core histones.ConclusionsComparison of the telomerase deletion transcription responses by Saccharomyces cerevisiae and H. polymorpha demonstrates that senescence makes different impact on the main metabolic pathways of these yeast species but induces similar changes in processes related to nucleic acids metabolism and protein synthesis. Up-regulation of a subunit of the TORC1 complex is clearly relevant for both types of yeast.

Highlights

In the course of replication of eukaryotic chromosomes, the telomere length is maintained due to activity of telomerase, the ribonucleoprotein reverse transcriptase
We focused our research on a telomerase from the thermotolerant yeast, Hansenula polymorpha DL-1, which is able to grow at temperatures up to 50 °C [13]
Such early senescence onset has been previously observed [16], and most likely stems from shorter telomeres in H. polymorpha DL-1 compared to S. cerevisiae [14]

Summary

Introduction

In the course of replication of eukaryotic chromosomes, the telomere length is maintained due to activity of telomerase, the ribonucleoprotein reverse transcriptase. Another vital function of telomeres is to solve the problem of incomplete replication of linear chromosomes, which arises due to the inability of DNA polymerases to fully replicate chromosome ends [1] In eukaryotes, this problem is solved due to telomerase, a special enzyme complex that through the activity of its reverse transcriptase (TERT) uses an RNA template (TER) to add tandem repeats of a simple telomeric DNA sequence to the chromosome ends. This problem is solved due to telomerase, a special enzyme complex that through the activity of its reverse transcriptase (TERT) uses an RNA template (TER) to add tandem repeats of a simple telomeric DNA sequence to the chromosome ends Upon synthesis of this extension, the DNA polymerases can replicate the complementary strand, Beletsky et al BMC Genomics (2017) 18:492 creating a double-stranded DNA molecule [1]. In yeast Saccharomyces cerevisiae the length of telomeres is about 350 bp, while human telomeres span several thousand base pairs

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