Regulation of Telomerase Reverse Transcriptase Gene in Human Cells

Telomeres are specialized structures at the ends of chromosomes. In humans, telomeres consist of hundreds to thousands of tandem repeats of the sequence TTAGGG which are bound by specific proteins including POT1, TRF1, TRF2, Rap1, TIN2 and TPP1. Functional telomeres protect chromosomal ends from DNA degradation and unwanted recombination, and are known to play an important role in cellular senescence. The most versatile and widely used method of telomere length maintenance is based on telomerase, a specialized ribonucleoprotein reverse transcriptase that directs the synthesis of telomeric repeats at chromosome ends. Telomerase is stringently repressed in normal human somatic cells but reactivated in cancers and in immortal cells, linking this enzyme with cell immortality and carcinogenesis. Several lines of evidence indicate that the expression of human telomerase reverse transcriptase (hTERT) is the rate-limiting step governing the overall telomerase activity. As yet, the molecular details of hTERT gene regulation remain poorly understood. In this application, we propose: (i) to identify and characterize the hTERT regulators by genome-wide RNAi screening, and (ii) to explore the involvement of microRNAs in the regulation of hTERT..

Project ID:PA9908-0478
External Project ID:NSC99-2311-B182-003-MY3