Abstract IA-23: TERT, senescence, and transformation

Abstract

Abstract Constitutive expression of telomerase in human cells prevents the onset of senescence and crisis by maintaining telomere homeostasis. However, accumulating evidence suggests that the human telomerase catalytic subunit (hTERT) contributes to cell physiology independent of its ability to elongate telomeres. We have recently found that hTERT interacts with the RNA component of mitochondrial RNA processing endoribonuclease (RMRP), a gene that is mutated in the inherited pleiotropic syndrome Cartilage-Hair Hypoplasia (CHH). hTERT and RMRP form a distinct ribonucleoprotein complex that exhibits RNA dependent RNA polymerase (RdRP) activity and produces double-stranded RNAs that can be processed into small interfering RNA in a Dicer-dependent manner. These observations identify a mammalian RdRP composed of hTERT in complex with RMRP. Since mutations in RMRP are found in CHH, these findings suggest that perturbation of the hTERT-RMRP complex is involved in the pathogenesis of this disorder. The involvement of hTERT in two syndromes characterized by stem cell failure (CHH and dyskeratosis congenita) suggests that ribonucleoprotein complexes containing hTERT play a critical role in stem cell biology. Citation Information: Cancer Res 2009;69(23 Suppl):IA-23.