TY - JOUR

T1 - The genome-wide transcription response to telomerase deficiency in the thermotolerant yeast Hansenula polymorpha DL-1

AU - Beletsky, Alexey V.

AU - Malyavko, Alexander N.

AU - Sukhanova, Maria V.

AU - Mardanova, Eugenia S.

AU - Zvereva, Maria I.

AU - Petrova, Olga A.

AU - Parfenova, Yulia Yu

AU - Rubtsova, Maria P.

AU - Mardanov, Andrey V.

AU - Lavrik, Olga I.

AU - Dontsova, Olga A.

AU - Ravin, Nikolai V.

N1 - Publisher Copyright: © 2017 The Author(s).

PY - 2017/6/28

Y1 - 2017/6/28

N2 - Background: In 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. Results: Mutant 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. Conclusions: Comparison 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.

AB - Background: In 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. Results: Mutant 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. Conclusions: Comparison 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.

KW - Autophagy

KW - DNA repair

KW - Environmental stress response

KW - Hansenula polymorpha

KW - RNA-seq

KW - Senescence

KW - Telomerase

KW - Yeast

KW - Carbohydrate Metabolism/genetics

KW - DNA Damage/genetics

KW - Genomics

KW - Telomere Shortening/genetics

KW - Energy Metabolism/genetics

KW - Pichia/cytology

KW - Genes, Fungal/genetics

KW - RNA, Messenger/genetics

KW - Autophagy/genetics

KW - Stress, Physiological/genetics

KW - Intracellular Space/metabolism

KW - Environment

KW - Transcription, Genetic

KW - Thermotolerance

KW - Telomerase/deficiency

KW - DNA-DAMAGE RESPONSE

KW - BINDING-PROTEIN

KW - LENGTH REGULATION

KW - SACCHAROMYCES-CEREVISIAE

KW - BUDDING YEAST

KW - DOUBLE-STRAND BREAKS

KW - MAINTENANCE

KW - INDUCED REPLICATION

KW - UNCAPPED TELOMERES

KW - CHROMOSOME END PROTECTION

UR - http://www.scopus.com/inward/record.url?scp=85021332636&partnerID=8YFLogxK

U2 - 10.1186/s12864-017-3889-x

DO - 10.1186/s12864-017-3889-x

M3 - Article

C2 - 28659185

AN - SCOPUS:85021332636

VL - 18

SP - 492

JO - BMC Genomics

JF - BMC Genomics

SN - 1471-2164

IS - 1

M1 - 492

ER -