Mammalian Telomerase: Catalytic Subunit and Knockout Mice

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Abstract
For the second time this year random cDNA sequencing, in combination with data from unicellular eukaryotes, has made a significant contribution to the analysis of human telomerase. Two groups have reported mammalian homologues of the Tetrahymena p80 telomerase-associated protein, in both cases the key breakthrough being mammalian cDNA clones with database matches to Tetrahymena p80. This has now been joined by the sequence of a candidate for the human telomerase catalytic subunit. The discovery that its message abundance closely follows telomerase activity could make a major impact on the utility of telomerase as a diagnostic marker for human malignancy. In addition, Blasco et al. report the phenotype of a transgenic mouse deleted for the mTR gene, which encodes the essential RNA component of telomerase. Interestingly tumour formation is unaffected in these mice, strengthening the argument that telomerase expression in mouse tumourigenesis is an innocent bystander rather than a necessary event. However, fundamental differences between the genomic organisation of mouse and human telomeres mean that the mouse is not a straightforward model to critically test the role of telomere loss and telomerase in human malignancy.