Telomerase reverse transcriptase (TERT)

Telomerase reverse transcriptase is the catalytic protein subunit essential for the function of the enzyme telomerase, a ribonucleoprotein complex responsible for maintaining chromosome ends by adding repetitive TTAGGG sequences to telomeres. This process is crucial for genome stability during cell division. The enzyme consists primarily of two core components: TERT itself—a specialized reverse transcriptase—and an integral RNA template known as TERC. While most somatic cells repress TERT expression after development—leading to progressive shortening and eventual loss-of-function at chromosomal ends—stem cells, germline cells, and especially cancerous cells often maintain high levels of active hTERT. This enables unlimited replicative potential characteristic of malignancy. Structurally, human TERT contains unique N-terminal and C-terminal extensions flanking a central RT-like domain with conserved motifs required for its enzymatic function. It forms part of a larger holoenzyme complex with additional proteins necessary for biogenesis, localization, recruitment to chromosome ends via shelterin proteins like TPP1, and processive repeat synthesis. Because reactivation or upregulation occurs in over 85%–90% percent of human cancers, telomerase reverse transcriptase is considered an important therapeutic target both experimentally and clinically; several small molecules are under investigation as direct inhibitors. However, systemic inhibition poses risks due to possible adverse effects on normal regenerative tissues.

Other names

TERThTERT (for human telomerase reverse transcriptase)Telomerase catalytic subunitTelomerase RNA-dependent DNA polymerase

Drugs targeting this molecule typically act by one or more of the following mechanisms: Direct inhibition of the enzymatic activity of TERT/telomerase, preventing addition of TTAGGG repeats to chromosome ends. Disruption of the assembly or stability of the telomerase holoenzyme complex. Induction of alternative splicing variants that lack catalytic activity.