Unraveling the stepwise maturation of the yeast telomerase including a Cse1 and Mtr10 mediated quality control checkpoint

Abstract Telomerases elongate the ends of chromosomes required for cell immortality through their reverse transcriptase activity. By using the model organism Saccharomyces cerevisiae we defined the order in which the holoenzyme matures. First, a longer precursor of the telomerase RNA, TLC1 is transc...

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Autores principales:	Anna Greta Hirsch, Daniel Becker, Jan-Philipp Lamping, Heike Krebber
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/4377d5e1eb81413e8797c3d7b71c3737
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spelling	oai:doaj.org-article:4377d5e1eb81413e8797c3d7b71c37372021-11-14T12:19:00ZUnraveling the stepwise maturation of the yeast telomerase including a Cse1 and Mtr10 mediated quality control checkpoint10.1038/s41598-021-01599-32045-2322https://doaj.org/article/4377d5e1eb81413e8797c3d7b71c37372021-11-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-01599-3https://doaj.org/toc/2045-2322Abstract Telomerases elongate the ends of chromosomes required for cell immortality through their reverse transcriptase activity. By using the model organism Saccharomyces cerevisiae we defined the order in which the holoenzyme matures. First, a longer precursor of the telomerase RNA, TLC1 is transcribed and exported into the cytoplasm, where it associates with the protecting Sm-ring, the Est and the Pop proteins. This partly matured telomerase is re-imported into the nucleus via Mtr10 and a novel TLC1-import factor, the karyopherin Cse1. Remarkably, while mutations in all known transport factors result in short telomere ends, mutation in CSE1 leads to the amplification of Y′ elements in the terminal chromosome regions and thus elongated telomere ends. Cse1 does not only support TLC1 import, but also the Sm-ring stabilization on the RNA enableling Mtr10 contact and nuclear import. Thus, Sm-ring formation and import factor contact resembles a quality control step in the maturation process of the telomerase. The re-imported immature TLC1 is finally trimmed into the 1158 nucleotides long mature form via the nuclear exosome. TMG-capping of TLC1 finalizes maturation, leading to mature telomerase.Anna Greta HirschDaniel BeckerJan-Philipp LampingHeike KrebberNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-18 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Anna Greta Hirsch Daniel Becker Jan-Philipp Lamping Heike Krebber Unraveling the stepwise maturation of the yeast telomerase including a Cse1 and Mtr10 mediated quality control checkpoint
description	Abstract Telomerases elongate the ends of chromosomes required for cell immortality through their reverse transcriptase activity. By using the model organism Saccharomyces cerevisiae we defined the order in which the holoenzyme matures. First, a longer precursor of the telomerase RNA, TLC1 is transcribed and exported into the cytoplasm, where it associates with the protecting Sm-ring, the Est and the Pop proteins. This partly matured telomerase is re-imported into the nucleus via Mtr10 and a novel TLC1-import factor, the karyopherin Cse1. Remarkably, while mutations in all known transport factors result in short telomere ends, mutation in CSE1 leads to the amplification of Y′ elements in the terminal chromosome regions and thus elongated telomere ends. Cse1 does not only support TLC1 import, but also the Sm-ring stabilization on the RNA enableling Mtr10 contact and nuclear import. Thus, Sm-ring formation and import factor contact resembles a quality control step in the maturation process of the telomerase. The re-imported immature TLC1 is finally trimmed into the 1158 nucleotides long mature form via the nuclear exosome. TMG-capping of TLC1 finalizes maturation, leading to mature telomerase.
format	article
author	Anna Greta Hirsch Daniel Becker Jan-Philipp Lamping Heike Krebber
author_facet	Anna Greta Hirsch Daniel Becker Jan-Philipp Lamping Heike Krebber
author_sort	Anna Greta Hirsch
title	Unraveling the stepwise maturation of the yeast telomerase including a Cse1 and Mtr10 mediated quality control checkpoint
title_short	Unraveling the stepwise maturation of the yeast telomerase including a Cse1 and Mtr10 mediated quality control checkpoint
title_full	Unraveling the stepwise maturation of the yeast telomerase including a Cse1 and Mtr10 mediated quality control checkpoint
title_fullStr	Unraveling the stepwise maturation of the yeast telomerase including a Cse1 and Mtr10 mediated quality control checkpoint
title_full_unstemmed	Unraveling the stepwise maturation of the yeast telomerase including a Cse1 and Mtr10 mediated quality control checkpoint
title_sort	unraveling the stepwise maturation of the yeast telomerase including a cse1 and mtr10 mediated quality control checkpoint
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/4377d5e1eb81413e8797c3d7b71c3737
work_keys_str_mv	AT annagretahirsch unravelingthestepwisematurationoftheyeasttelomeraseincludingacse1andmtr10mediatedqualitycontrolcheckpoint AT danielbecker unravelingthestepwisematurationoftheyeasttelomeraseincludingacse1andmtr10mediatedqualitycontrolcheckpoint AT janphilipplamping unravelingthestepwisematurationoftheyeasttelomeraseincludingacse1andmtr10mediatedqualitycontrolcheckpoint AT heikekrebber unravelingthestepwisematurationoftheyeasttelomeraseincludingacse1andmtr10mediatedqualitycontrolcheckpoint
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Unraveling the stepwise maturation of the yeast telomerase including a Cse1 and Mtr10 mediated quality control checkpoint

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