The telomerase-specific T motif is a restrictive determinant of repetitive reverse transcription by human telomerase.

Molecular and Cellular Biology
William C Drosopoulos, Vinayaka R Prasad

Abstract

The central hallmark of telomerases is repetitive copying of a short, defined sequence within its integral RNA subunit. We sought to identify structural determinants of this unique activity in the catalytic protein subunit telomerase reverse transcriptase (TERT) of telomerase. Residues within the highly conserved telomerase-specific T motif of human TERT were mutationally probed, leading to variant telomerases with increased repeat extension rates and wild-type processivity. The extension rate increases were independent of template sequence composition and only moderately correlated to telomerase RNA (TR) binding. Importantly, analysis of substrate primer elongation showed that the extension rate increases primarily resulted from increases in the repeat (type II) translocation rate. Our findings indicate a participatory role for the T motif in repeat translocation, an obligatory event for repetitive telomeric DNA synthesis. Thus, the T motif serves as a restrictive determinant of repetitive reverse transcription.

References

Aug 1, 1985·Proceedings of the National Academy of Sciences of the United States of America·I A WilsonS Brenner
Jul 1, 1993·Genes & Development·K Collins, C W Greider
Oct 1, 1993·Molecular and Cellular Biology·M S Lee, E H Blackburn
Sep 15, 1997·Nucleic Acids Research·P W Hammond, T R Cech
Jul 22, 1998·Proceedings of the National Academy of Sciences of the United States of America·T M BryanT R Cech
Jul 22, 1998·Proceedings of the National Academy of Sciences of the United States of America·K Collins, L Gandhi
Oct 12, 2000·Molecular Biology of the Cell·T L BeattieL Harrington
Nov 30, 2000·The Journal of Biological Chemistry·C D HardyK Collins
Feb 7, 2001·Molecular and Cellular Biology·C K LaiK Collins
May 9, 2001·Biochimica Et Biophysica Acta·W GuoN H Park
Feb 19, 2002·Genes & Development·Cary K LaiKathleen Collins
Aug 2, 2002·The Journal of Biological Chemistry·Shabbir HossainNeal F Lue
Jul 11, 2003·Nucleic Acids Research·Sylvain HuardChantal Autexier
Apr 7, 2004·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Simon R W L Chan, Elizabeth H Blackburn
Sep 8, 2004·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Neal F Lue
Feb 26, 2005·The Journal of Biological Chemistry·Catherine M O'ConnorKathleen Collins
May 21, 2005·The Journal of Biological Chemistry·Neal F Lue
Aug 3, 2005·The Journal of Biological Chemistry·William C DrosopoulosVinayaka R Prasad
Feb 8, 2006·Nature Structural & Molecular Biology·Steven A JacobsThomas R Cech
Jun 8, 2006·Annual Review of Biochemistry·Chantal Autexier, Neal F Lue
Jul 11, 2006·Nature Reviews. Molecular Cell Biology·Kathleen Collins
Feb 14, 2007·Molecular and Cellular Biology·Haley D M WyattTara L Beattie
Sep 2, 2008·Nature·Andrew J GillisEmmanuel Skordalakes

❮ Previous
Next ❯

Citations

Nov 30, 2011·Proceedings of the National Academy of Sciences of the United States of America·Christopher J BleyJulian J-L Chen
May 13, 2010·Nucleic Acids Research·Haley D M WyattTara L Beattie
Aug 6, 2011·Current Opinion in Chemical Biology·Kathleen Collins
Apr 5, 2013·The FEBS Journal·Kyle R Hukezalie, Judy M Y Wong
Dec 21, 2010·Current Opinion in Structural Biology·Mark MasonEmmanuel Skordalakes
Apr 2, 2010·Nature Structural & Molecular Biology·Meghan MitchellEmmanuel Skordalakes
Nov 20, 2015·Nature Structural & Molecular Biology·Wei Yang, Young-Sam Lee
Feb 15, 2018·The EMBO Journal·Yinnan ChenJulian J-L Chen
Nov 25, 2020·Proceedings of the National Academy of Sciences of the United States of America·Yaqiang WangJuli Feigon

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.