Intracellular trafficking of yeast telomerase components
Reads0
Chats0
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
More filters
Journal ArticleDOI
Regulation of Telomerase by Telomeric Proteins
TL;DR: The details of telomerase and its regulation by the telomere are discussed, including single-stranded DNA-binding proteins (POT1 in humans and Cdc13 in budding yeast), which have been proposed to contribute to the recruitment of telomersase and may also regulate the extent or frequency of elongation.
Journal ArticleDOI
Telomere Length Homeostasis Is Achieved via a Switch between Telomerase- Extendible and -Nonextendible States
TL;DR: It is demonstrated that telomere length homeostasis is achieved via a switch between telomerase-extendible and -nonextendible states by taking a molecular snapshot of a single round of telomeres replication.
Journal ArticleDOI
Beginning to Understand the End of the Chromosome
TL;DR: Since the discovery of an enzyme that extended the DNA at chromosome telomeres in the ciliate, Tetrahymena, there has been an explosion of knowledge about both the RNA and protein subunits of this unusual ribonucleoprotein enzyme.
Journal ArticleDOI
Telomere length homeostasis requires that telomerase levels are limiting.
TL;DR: Concomitant overexpression of TERT and TR was necessary and sufficient to substantially increase telomerase activity, and in less than 50 PDs, the length of telomeres increased 3–8‐fold beyond physiological size, while telomere‐bound TRF1 and TRF2 increased proportionally to telomer length.
Journal ArticleDOI
The biogenesis and regulation of telomerase holoenzymes
TL;DR: Insights that have been gained into the cellular pathways for biogenesis and regulation of telomerase ribonucleoproteins raise new questions, particularly concerning the dynamic nature of this unique polymerase.
References
More filters
Journal ArticleDOI
Essential regions of Saccharomyces cerevisiae telomerase RNA: separate elements for Est1p and Est2p interaction.
TL;DR: The results support a role for the telomerase RNA serving as a scaffold for binding key protein subunits and having the RNA secured to the protein away from the template is proposed to facilitate the translocation of the RNA template through the active site.
Journal ArticleDOI
The Est1 Subunit of Yeast Telomerase Binds the Tlc1 Telomerase RNA
TL;DR: The data suggest that an important role of Est1 in the telomerase complex is to bind to the Tlc1 telomersase RNA via an RRM, and since Est1 can also bind telomeric DNA, Est1 may tether telomer enzyme to the telomere.
Journal ArticleDOI
Two functionally distinct domains generated by in vivo cleavage of Nup145p: a novel biogenesis pathway for nucleoporins
Maria Teresa Teixeira,Symeon Siniossoglou,Sasha Podtelejnikov,Jean Claude Bénichou,Mattias Mann,Bernard Dujon,Ed Hurt,Emmanuelle Fabre +7 more
TL;DR: It is demonstrated here that Nup145p is cleaved in vivo to yield two functionally distinct domains: a carboxy‐terminal domain (C‐N up145p) which is located at the nuclear pore complex (NPC) and assembles into the Nup84p complex, and a GLFG‐containing amino‐terminals of N‐Nup 145p which is not part of this complex.
Journal Article
The snoRNA domain of vertebrate telomerase RNA functions to localize the RNA within the nucleus.
TL;DR: It is suggested that the H/ACA motif confers functional localization of vertebrate telomerase RNAs to the nucleus, the compartment where telomeres are synthesized.
Journal ArticleDOI
Separate domains of KAR1 mediate distinct functions in mitosis and nuclear fusion.
TL;DR: A deletion analysis demonstrating that the mitotic and karyogamy functions of KAR1 are separate and independent, residing in discrete functional domains is reported and a model for Kar1p in which the protein is composed of several protein-binding domains tethered to the nuclear envelope via its hydrophobic tail is proposed.