Constitutive and regulated expression of telomerase reverse transcriptase (hTERT) in human lymphocytes

Human telomerase consists of two essential components, telomerase RNA templ ate (hTER) and telomerase reverse transcriptase (hTERT), and functions to s ynthesize telomere repeats that serve to protect the integrity of chromosom es and to prolong the replicative life span of cells. Telomerase activity i s expressed selectively in germ-line and malignant tumor cells but not in m ost normal human somatic cells. As a notable exception, telomerase is expre ssed in human lymphocytes during development, differentiation, and activati on. Recent studies have suggested that regulation of telomerase is determin ed by transcription of hTERT but not hTER. The highly regulated expression of telomerase in lymphocytes provides an opportunity to analyze the contrib ution of transcriptional regulation of hTERT and hTER. We report here an an alysis of hTERT expression by Northern and ill situ hybridization. It was f ound that hTERT mRNA is expressed at detectable levels in all subsets of hu man lymphocytes isolated from thymus, tonsil, and peripheral blood, regardl ess of the status of telomerase activity. hTERT expression is regulated as a function of lineage development, differentiation, and activation. Strikin gly, however, telomerase activity in these cells is not correlated strictly with the levels of hTERT and hTER transcripts. The absence of correlation between telomerase activity and hTERT mRNA could not be attributed to the p resence of hTERT splice variants or to detectable inhibitors of telomerase activity. Thus, transcriptional regulation of hTERT is not sufficient to ac count for telomerase activity in human lymphocytes, indicating a likely rol e of posttranscriptional factors in the control of enzyme function.