Cross species activity of TERT human telomerase component

Telomerase is a cellular enzyme that adds telomeric DNA sequences to the ends of chromosomes, aiding in preserving genome stability. The enzyme is formed by a protein with reverse transcriptase activity (TERT) and an RNA molecule that provides the sequence used as a template (TERC). These two components must interact precisely for telomerase to function, and their compatibility varies across species. Understanding whether the human protein component can function with the RNA molecules of other species is important for the development of therapies that activate telomerase, particularly those aimed at treating disorders associated with short telomeres. Here, we investigate the ability of the human TERT to interact with the telomerase RNA from several mammalian species commonly used in preclinical research, including monkey, pig, dog, rabbit, rat, and mouse. We introduced the human TERT into primary lung fibroblasts from each species and assessed its capacity to generate telomeric repeats in cell extracts. We also analyzed telomere length during extended cell culture to determine whether telomeres lengthened over time. Human TERT formed an active complex with the telomerase RNA from monkey, pig, rabbit, and rat in vitro, but not with that from dog or mouse. However, only monkey and human cells showed progressive telomere lengthening during long-term culture. These results reveal that only non-human primate cells support full functional activity of the human telomerase protein in a cellular context, underscoring their suitability as preclinical models for telomerase-based therapeutic strategies.