Insights into the structure and function of Est3 from the Hansenula polymorpha telomerase

Abstract Telomerase is a ribonucleoprotein enzyme, which maintains genome integrity in eukaryotes and ensures continuous cellular proliferation. Telomerase holoenzyme from the thermotolerant yeast Hansenula polymorpha, in addition to the catalytic subunit (TERT) and telomerase RNA (TER), contains ac...

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Autores principales:	Nikita M. Shepelev, Sofia S. Mariasina, Alexey B. Mantsyzov, Alexander N. Malyavko, Sergey V. Efimov, Olga A. Petrova, Elena V. Rodina, Maria I. Zvereva, Olga A. Dontsova, Vladimir I. Polshakov
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c30a64ef786b423ca96996243d680aa3
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spelling	oai:doaj.org-article:c30a64ef786b423ca96996243d680aa32021-12-02T15:39:39ZInsights into the structure and function of Est3 from the Hansenula polymorpha telomerase10.1038/s41598-020-68107-x2045-2322https://doaj.org/article/c30a64ef786b423ca96996243d680aa32020-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-68107-xhttps://doaj.org/toc/2045-2322Abstract Telomerase is a ribonucleoprotein enzyme, which maintains genome integrity in eukaryotes and ensures continuous cellular proliferation. Telomerase holoenzyme from the thermotolerant yeast Hansenula polymorpha, in addition to the catalytic subunit (TERT) and telomerase RNA (TER), contains accessory proteins Est1 and Est3, which are essential for in vivo telomerase function. Here we report the high-resolution structure of Est3 from Hansenula polymorpha (HpEst3) in solution, as well as the characterization of its functional relationships with other components of telomerase. The overall structure of HpEst3 is similar to that of Est3 from Saccharomyces cerevisiae and human TPP1. We have shown that telomerase activity in H. polymorpha relies on both Est3 and Est1 proteins in a functionally symmetrical manner. The absence of either Est3 or Est1 prevents formation of a stable ribonucleoprotein complex, weakens binding of a second protein to TER, and decreases the amount of cellular TERT, presumably due to the destabilization of telomerase RNP. NMR probing has shown no direct in vitro interactions of free Est3 either with the N-terminal domain of TERT or with DNA or RNA fragments mimicking the probable telomerase environment. Our findings corroborate the idea that telomerase possesses the evolutionarily variable functionality within the conservative structural context.Nikita M. ShepelevSofia S. MariasinaAlexey B. MantsyzovAlexander N. MalyavkoSergey V. EfimovOlga A. PetrovaElena V. RodinaMaria I. ZverevaOlga A. DontsovaVladimir I. PolshakovNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-17 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Nikita M. Shepelev Sofia S. Mariasina Alexey B. Mantsyzov Alexander N. Malyavko Sergey V. Efimov Olga A. Petrova Elena V. Rodina Maria I. Zvereva Olga A. Dontsova Vladimir I. Polshakov Insights into the structure and function of Est3 from the Hansenula polymorpha telomerase
description	Abstract Telomerase is a ribonucleoprotein enzyme, which maintains genome integrity in eukaryotes and ensures continuous cellular proliferation. Telomerase holoenzyme from the thermotolerant yeast Hansenula polymorpha, in addition to the catalytic subunit (TERT) and telomerase RNA (TER), contains accessory proteins Est1 and Est3, which are essential for in vivo telomerase function. Here we report the high-resolution structure of Est3 from Hansenula polymorpha (HpEst3) in solution, as well as the characterization of its functional relationships with other components of telomerase. The overall structure of HpEst3 is similar to that of Est3 from Saccharomyces cerevisiae and human TPP1. We have shown that telomerase activity in H. polymorpha relies on both Est3 and Est1 proteins in a functionally symmetrical manner. The absence of either Est3 or Est1 prevents formation of a stable ribonucleoprotein complex, weakens binding of a second protein to TER, and decreases the amount of cellular TERT, presumably due to the destabilization of telomerase RNP. NMR probing has shown no direct in vitro interactions of free Est3 either with the N-terminal domain of TERT or with DNA or RNA fragments mimicking the probable telomerase environment. Our findings corroborate the idea that telomerase possesses the evolutionarily variable functionality within the conservative structural context.
format	article
author	Nikita M. Shepelev Sofia S. Mariasina Alexey B. Mantsyzov Alexander N. Malyavko Sergey V. Efimov Olga A. Petrova Elena V. Rodina Maria I. Zvereva Olga A. Dontsova Vladimir I. Polshakov
author_facet	Nikita M. Shepelev Sofia S. Mariasina Alexey B. Mantsyzov Alexander N. Malyavko Sergey V. Efimov Olga A. Petrova Elena V. Rodina Maria I. Zvereva Olga A. Dontsova Vladimir I. Polshakov
author_sort	Nikita M. Shepelev
title	Insights into the structure and function of Est3 from the Hansenula polymorpha telomerase
title_short	Insights into the structure and function of Est3 from the Hansenula polymorpha telomerase
title_full	Insights into the structure and function of Est3 from the Hansenula polymorpha telomerase
title_fullStr	Insights into the structure and function of Est3 from the Hansenula polymorpha telomerase
title_full_unstemmed	Insights into the structure and function of Est3 from the Hansenula polymorpha telomerase
title_sort	insights into the structure and function of est3 from the hansenula polymorpha telomerase
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/c30a64ef786b423ca96996243d680aa3
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Insights into the structure and function of Est3 from the Hansenula polymorpha telomerase

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