“…Interestingly, splicing variants that lack the a site function as dominant-negative inhibitors of telomerase causing telomere shortening and eventually cell death (Colgin et al, 2000;Yi et al, 2000). In an analysis of clinical samples, tumors expressing splicing variants of hTERT have been shown to lack telomerase activity (Ulaner et al, 2000). However, some normal tissues with hTERT transcripts containing both a and b lack telomerase activity (Ulaner et al, 2000), suggesting that there are further mechanisms for suppressing telomerase activity downstream of hTERT transcription and mRNA splicing, and these mechanisms have been lost during neoplastic transformation.…”