Posttranscriptional regulation of telomerase reverse transcriptase in Human T cells

Telomerase, a reverse transcriptase consisting of a catalytic subunit (TERT) and a RNA template (TERC), plays an essential role in maintaining the length of telomeres and cellular replicative lifespan. TERT mRNA is present in resting human T cells but with undetectable level of telomerase activity. It is unclear whether the lack of telomerase activity is a result of non‐functional Alternate Splicing Products (ASP) of TERT mRNA and/or missing proper post‐translational modifications of TERT protein. It was hypothesized that missing proper post‐translational modifications of TERT protein lead to the lack of telomerase activity. We analyzed two common TERT splicing forms in resting and activated human T cell subsets using single cell RT‐PCR method. We found that 1) 39% of the resting T cells expressed TERT full‐length alone, 34% expressed both full‐length and ASP and 27% expressed only ASP; 2) activation decreased expression of full‐length TERT and increased expression of ASP; and 3) all live and dead T cells after activation had ASP. These findings show that resting T cells express mostly full‐length TERT whereas activated T cells express mostly ASP. Further studies will be needed to elucidate this seemingly paradoxical finding. The findings of this study may lead to pharmaceutical interventions to slow or stop the aging process.