The Structure and Function of Telomerase Reverse Transcriptase

Abstract

The structure and integrity of telomeres are essential for genome stability. Telomere dysregulation can lead to cell death, cell senescence, or abnormal cell proliferation. The maintenance of telomere repeats in most eukaryotic organisms requires telomerase, which consists of a reverse transcriptase (RT) and an RNA template that dictates the synthesis of the G-rich strand of telomere terminal repeats. Structurally, telomerase reverse transcriptase (TERT) contains unique and variable N- and C-terminal extensions that flank a central RT-like domain. The enzymology of telomerase includes features that are both similar to and distinct from those characteristic of other RTs. Two distinguishing features of TERT are its stable association with the telomerase RNA and its ability to repetitively reverse transcribe the template segment of RNA. Here we discuss TERT structure and function; its regulation by RNA-DNA, TERT-DNA, TERT-RNA, TERT-TERT interactions, and TERT-associated proteins; and the relationship between telomerase enzymology and telomere maintenance.

Telomere Shortening in Familial and Sporadic Pulmonary Fibrosis

“…One of the patients with sporadic disease had a missense mutation in the C-terminal region of TERT (S957R). All of these missense mutations involve highly conserved residues in regions of the protein ( Figures 1B and 1C) that have postulated roles in enzymatic activity, processivity, and cellular location of the protein (15)(16)(17). None of the mutations were detected in a multiethnic panel of 528 individuals sequenced as control subjects (8).…”

Frequent changes in subtelomeric DNA methylation patterns and its relevance to telomere regulation during human hepatocarcinogenesis

“…Telomerase adds telomeric repeat sequences to the 3 0 end of telomeres. 6 Most cancer cells possess active telomerase, and thus, telomere length is maintained during successive proliferation. 7,8 In telomerase-negative cancer cells, telomere is maintained by telomere recombination, which results in long telomeres with heterogeneity.…”

Telomerase caught in the act

“…In order to counteract this telomere attrition, virtually all eukaryotic cells contain an end specialized enzyme called telomerase. 3 The telomerase holoenzyme is a ribonucleoprotein complex that possesses a reverse-transcriptase activity and carries its own RNA template. 4 In budding yeast, the RNA component of telomerase is called TLC1 and is used as a scaffold for the binding of the catalytic subunit (Est2) and several regulatory proteins, such as Est1, Est3 and the yKu70/80 complex.…”

“…1 In the budding yeast Saccharomyces cerevisiae, telomeres are composed of degenerated TG [1][2][3] repeats bound by specific telomere binding proteins. 2 Due to inherent problems replicating DNA ends, telomeric…”