scholarly journals A universal telomerase RNA core structure includes structured motifs required for binding the telomerase reverse transcriptase protein

2004 ◽  
Vol 101 (41) ◽  
pp. 14713-14718 ◽  
Author(s):  
J. Lin ◽  
H. Ly ◽  
A. Hussain ◽  
M. Abraham ◽  
S. Pearl ◽  
...  
Keyword(s):  
Reverse Transcriptase ◽  
Core Structure ◽  
Telomerase Reverse Transcriptase ◽  
Telomerase Rna ◽  
Structured Motifs

scholarly journals Telomerase Activity Reconstitutedin Vitrowith Purified Human Telomerase Reverse Transcriptase and Human Telomerase RNA Component

2000 ◽  
Vol 275 (29) ◽  
pp. 22568-22573 ◽  
Author(s):  
Kenkichi Masutomi ◽  
Shuichi Kaneko ◽  
Naoyuki Hayashi ◽  
Tatsuya Yamashita ◽  
Yukihiro Shirota ◽  
...  
Keyword(s):  
Reverse Transcriptase ◽  
Telomerase Activity ◽  
Telomerase Reverse Transcriptase ◽  
Telomerase Rna ◽  
Human Telomerase Reverse Transcriptase ◽  
Human Telomerase

scholarly journals Telomerase biogenesis requires a novel Mex67 function and a cytoplasmic association with the Sm7 complex

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Yulia Vasianovich ◽  
Emmanuel Bajon ◽  
Raymund J Wellinger
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Life Cycle ◽  
Reverse Transcriptase ◽  
Nuclear Export ◽  
Complex Life Cycle ◽  
Telomerase Reverse Transcriptase ◽  
Telomerase Rna ◽  
The Core ◽  
Nuclear Stability

The templating RNA is the core of the telomerase reverse transcriptase. In Saccharomyces cerevisiae, the complex life cycle and maturation of telomerase includes a cytoplasmic stage. However, timing and reason for this cytoplasmic passage are poorly understood. Here, we use inducible RNA tagging experiments to show that immediately after transcription, newly synthesized telomerase RNAs undergo one round of nucleo-cytoplasmic shuttling. Their export depends entirely on Crm1/Xpo1, whereas re-import is mediated by Kap122 plus redundant, kinetically less efficient import pathways. Strikingly, Mex67 is essential to stabilize newly transcribed RNA before Xpo1-mediated nuclear export. The results further show that the Sm7 complex associates with and stabilizes the telomerase RNA in the cytoplasm and promotes its nuclear re-import. Remarkably, after this cytoplasmic passage, the nuclear stability of telomerase RNA no longer depends on Mex67. These results underscore the utility of inducible RNA tagging and challenge current models of telomerase maturation.

Telomerase Reverse Transcriptase (hTERT) mRNA and Telomerase RNA (hTR) as Targets for Downregulation of Telomerase Activity

2004 ◽  
Vol 14 (4) ◽  
pp. 263-273 ◽  
Author(s):  
Shobhana Natarajan ◽  
Zhi Chen ◽  
Edward V. Wancewicz ◽  
Brett P. Monia ◽  
David R. Corey
Keyword(s):  
Reverse Transcriptase ◽  
Telomerase Activity ◽  
Telomerase Reverse Transcriptase ◽  
Telomerase Rna ◽  
Htert Mrna

scholarly journals Tetrahymena Telomerase Protein p65 Induces Conformational Changes throughout Telomerase RNA (TER) and Rescues Telomerase Reverse Transcriptase and TER Assembly Mutants

2010 ◽  
Vol 30 (20) ◽  
pp. 4965-4976 ◽  
Author(s):  
Andrea J. Berman ◽  
Anne R. Gooding ◽  
Thomas R. Cech
Keyword(s):  
Reverse Transcriptase ◽  
Single Molecule ◽  
Conformational Changes ◽  
Mutational Analysis ◽  
Telomerase Activity ◽  
Telomerase Reverse Transcriptase ◽  
Telomerase Rna ◽  
Hierarchical Assembly ◽  
Family Protein ◽  
Catalytically Active

ABSTRACT The biogenesis of the Tetrahymena telomerase ribonucleoprotein particle (RNP) is enhanced by p65, a La family protein. Single-molecule and biochemical studies have uncovered a hierarchical assembly of the RNP, wherein the binding of p65 to stems I and IV of telomerase RNA (TER) causes a conformational change that facilitates the subsequent binding of telomerase reverse transcriptase (TERT) to TER. We used purified p65 and variants of TERT and TER to investigate the conformational rearrangements that occur during RNP assembly. Nuclease protection assays and mutational analysis revealed that p65 interacts with and stimulates conformational changes in regions of TER beyond stem IV. Several TER mutants exhibited telomerase activity only in the presence of p65, revealing the importance of p65 in promoting the correct RNP assembly pathway. In addition, p65 rescued TERT assembly mutants but not TERT activity mutants. Taken together, these results suggest that p65 stimulates telomerase assembly and activity in two ways. First, by sequestering stems I and IV, p65 limits the ensemble of structural conformations of TER, thereby presenting TERT with the active conformation of TER. Second, p65 acts as a molecular buttress within the assembled RNP, mutually stabilizing TER and TERT in catalytically active conformations.

scholarly journals Expression of Telomerase RNA Template, but Not Telomerase Reverse Transcriptase, Is Limiting for Telomere Length Maintenance In Vivo

2004 ◽  
Vol 24 (16) ◽  
pp. 7024-7031 ◽  
Author(s):  
Y. Jeffrey Chiang ◽  
Michael T. Hemann ◽  
Karen S. Hathcock ◽  
Lino Tessarollo ◽  
Lionel Feigenbaum ◽  
...  
Keyword(s):  
Reverse Transcriptase ◽  
Telomere Length ◽  
Telomerase Activity ◽  
Telomere Maintenance ◽  
Gene Copy ◽  
Telomerase Reverse Transcriptase ◽  
Telomerase Rna ◽  
Wild Type ◽  
Telomere Elongation

ABSTRACT Telomerase consists of two essential components, the telomerase RNA template (TR) and telomerase reverse transcriptase (TERT). The haplo-insufficiency of TR was recently shown to cause one form of human dyskeratosis congenita, an inherited disease marked by abnormal telomere shortening. Consistent with this finding, we recently reported that mice heterozygous for inactivation of mouse TR exhibit a similar haplo-insufficiency and are deficient in the ability to elongate telomeres in vivo. To further assess the genetic regulation of telomerase activity, we have compared the abilities of TR-deficient and TERT-deficient mice to maintain or elongate telomeres in interspecies crosses. Homozygous TERT knockout mice had no telomerase activity and failed to maintain telomere length. In contrast, TERT+/− heterozygotes had no detectable defect in telomere elongation compared to wild-type controls, whereas TR+/− heterozygotes were deficient in telomere elongation. Levels of TERT mRNA in heterozygous mice were one-third to one-half the levels expressed in wild-type mice, similar to the reductions in telomerase RNA observed in TR heterozygotes. These findings indicate that both TR and TERT are essential for telomere maintenance and elongation but that gene copy number and transcriptional regulation of TR, but not TERT, are limiting for telomerase activity under the in vivo conditions analyzed.

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