Telomerase reverse transcriptase complex (TERT) (TERT)

The telomerase reverse transcriptase complex is a specialized ribonucleoprotein enzyme responsible for maintaining the length of telomeres by adding repetitive DNA sequences (TTAGGG in humans) to the 3' ends of chromosomes (UniProt: O14746; NIH: Gene ID 7015). It primarily consists of two core components: the catalytic protein subunit, telomerase reverse transcriptase (TERT), and the integral telomerase RNA (TERC), which serves as the template for DNA synthesis (PubMed: PMC3312632). While telomerase is typically silenced in most adult somatic cells, it is highly active in germ cells, stem cells, and approximately 90% of human cancers, where it confers cellular immortality by bypassing the Hayflick limit (StatPearls: NBK541040). In oncology, therapeutic strategies focus on inhibiting telomerase to induce senescence and apoptosis in malignant cells, with agents like the oligonucleotide imetelstat targeting the RNA template (ClinicalTrials.gov: NCT03735550). Conversely, telomerase activation is being explored as a treatment for telomeropathies, such as idiopathic pulmonary fibrosis and aplastic anemia, where premature telomere shortening leads to organ failure (NEJM: 379:1151-1164). The complex also plays non-canonical roles in gene expression regulation and mitochondrial protection, which may contribute to its pro-survival effects in cancer (Nature Reviews Cancer: 12, 202–214).

Other names

TelomerasehTERTTelomere terminal transferaseRibonucleoprotein telomeraseHEST2

Competitive inhibition of the telomerase RNA template (TERC) to prevent telomere elongation, or induction of cytotoxic T-cell immune responses against TERT-derived peptides (PubMed: PMC3312632).