Intracellular trafficking of yeast telomerase components
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TLDR
It is found that Est1p, Est2p and TLC1 can migrate independently of each other to the nucleus and a role of the nucleolus in telomerase biogenesis is suggested.Abstract:
Telomerase uses an internal RNA moiety as template for the synthesis of telomere repeats. In Saccharomyces cerevisiae, the telomerase holoenzyme contains the telomerase reverse transcriptase subunit Est2p, the telomerase RNA moiety TLC1, the telomerase associated proteins Est1p and Est3p, and Sm proteins. Here we assess telomerase assembly by determining the localization of telomerase components. We found that Est1p, Est2p and TLC1 can migrate independently of each other to the nucleus. With limiting amounts of TLC1, overexpressed Est1p and Est2p accumulated in the nucleolus, whereas enzymatically active Est2p–TLC1 complexes are distributed over the entire nucleus. The distribution to the nucleoplasm depended on the specific interaction between Est2p and TLC1 but was independent of Est1p and Est3p. Altogether, our results suggest a role of the nucleolus in telomerase biogenesis. We also describe experiments that support a transient cytoplasmic localization of TLC1 RNA.read more
Citations
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Back to the future: The intimate and evolving connection between telomere-related factors and genotoxic stress
TL;DR: The relationship between oxidative stress and telomeres and the enigmatic role of telomere-associated proteins in mitochondria is considered, pointing to an evolving and intimate connection between telomerres and cellular physiology and the strong drive to maintain chromosome integrity.
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Curiously composite structures of a retrotransposon and a complex repeat associated with chromosome ends of Rhynchosciara americana (Diptera: Sciaridae).
TL;DR: The analyses performed raise the possibility that RaTART represents a genomic clone composed of distinct repetitive elements, one of which is likely to be responsible for its apparent enrichment at chromosome ends.
Journal ArticleDOI
Live-cell imaging of budding yeast telomerase RNA and TERRA.
TL;DR: Detailed protocols for live-cell imaging of the Saccharomyces cerevisiae telomerase RNA subunit, called TLC1, and also of the non-coding telomeric repeat-containing RNA TERRA are presented and the approach used for genomic integration of MS2 stem-loops in these transcripts is described.
Journal ArticleDOI
Normal telomere length maintenance in Saccharomyces cerevisiae requires nuclear import of the ever shorter telomeres 1 (Est1) protein via the importin alpha pathway.
TL;DR: It is suggested that at least two nuclear import pathways are required to achieve normal telomere length homeostasis in yeast.
Book ChapterDOI
11 – Telomeres and Telomerase Regulation
TL;DR: Telomerase has a crucial role in human hematopoietic stem cells and are strikingly illustrated by patients with the rare genetic disease dyskeratosis congenita (DKC).
References
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Journal ArticleDOI
A telomeric sequence in the RNA of Tetrahymena telomerase required for telomere repeat synthesis.
TL;DR: The essential RNA component of this ribonucleoprotein enzyme has now been cloned and found to contain the sequence CAACCCCAA, which seems to be the template for the synthesis of TTGGGG repeats.
Journal ArticleDOI
Reverse Transcriptase Motifs in the Catalytic Subunit of Telomerase
Joachim Lingner,Timothy P. Hughes,Andrej Shevchenko,Matthias Mann,Victoria Lundblad,Thomas R. Cech +5 more
TL;DR: The reverse transcriptase protein fold, previously known to be involved in retroviral replication and retrotransposition, is essential for normal chromosome telomere replication in diverse eukaryotes.
Journal ArticleDOI
A telomerase component is defective in the human disease dyskeratosis congenita
TL;DR: It is found that primary fibroblasts and lymphoblasts from DKC-affected males are not detectably deficient in conventional H/ACA small nucleolar RNA accumulation or function; however, DKC cells have a lower level of telomerase RNA, produce lower levels of telomersase activity and have shorter telomeres than matched normal cells.
Journal ArticleDOI
A mutant with a defect in telomere elongation leads to senescence in yeast.
TL;DR: Using this assay, a mutant that displays a progressive decrease in telomere length as well as an increased frequency of chromosome loss is isolated, which defines a new gene, designated EST1 (for ever shorter telomeres).
Journal ArticleDOI
Ribosome synthesis in Saccharomyces cerevisiae.
J. Venema,David Tollervey +1 more
TL;DR: The recent, and often surprising, advances in the understanding of ribosome synthesis in the yeast Saccharomyces cerevisiae will underscore the unexpected complexity of eukaryotic ribosomes synthesis.