Telomerase RNA component (TERC) template region (TERC)

The Telomerase RNA component (TERC) is a critical non-coding RNA molecule that serves as the structural scaffold and template for the telomerase holoenzyme (The RNA World, 2011). It contains a specific template region, typically 11 nucleotides long in humans, which provides the sequence for the synthesis of telomeric DNA repeats (TTAGGG) by the catalytic subunit, telomerase reverse transcriptase (TERT) (Shay & Wright, 2019, Nature Reviews Molecular Cell Biology). While telomerase activity is generally repressed in adult somatic cells, it is reactivated in approximately 90% of human cancers, facilitating cellular immortality and tumor progression (Townsley et al., 2014, Blood). Therapeutic targeting of the TERC template region, most notably by the oligonucleotide imetelstat, inhibits telomerase activity, leading to progressive telomere shortening and eventual apoptosis or senescence in malignant cells (Fenaux et al., 2020, Journal of Clinical Oncology). Beyond its role in oncology, germline mutations in the TERC gene are linked to telomere biology disorders, including dyskeratosis congenita and idiopathic pulmonary fibrosis, where insufficient telomere maintenance leads to bone marrow failure and organ dysfunction (Armanios & Blackburn, 2012, Nature Reviews Genetics).

Other names

hTRhTERCTelomerase RNATRTelomerase RNA component template region

Imetelstat is a lipid-conjugated oligonucleotide that binds with high affinity to the template region of the telomerase RNA component (TERC), acting as a competitive inhibitor to prevent telomerase activity and subsequent telomere elongation (Baerlocher et al., 2015, NEJM).