Tissue-specific alternate splicing of human telomerase reverse transcriptase (hTERT) influences telomere lengths during human development

Direct genetic manipulations have shown that telomerase-mediated telomere e longation plays a key role in determining cellular replicative capacity and senescence. The mechanisms regulating the production of an active telomera se enzyme are still predominantly unknown, although roles for transcription al control of hTERT, alternative-splicing of hTERT transcripts, and post-tr anslational phosphorylation of hTERT protein have been advocated. Here we s how that hTERT is alternatively spliced in specific patterns by different t issue types during human development. Alternative splicing often prohibits the expression of hTERT protein containing functional reverse transcriptase domains. In these instances, telomerase activity is absent, leading to sho rtening of telomeres. The specific pattern of hTERT mRNA variants in human development provides evidence that alternative splicing is non-random and p articipates in the regulation of telomerase activity. (C) 2001 Wiley-Liss, Inc.