Medical genetics and epigenetics of telomerase

Introduction Epigenetic regulation of telomerase: recent findings beyond transcriptional control Methylation Sirtuins Non-coding RNAs Consequences of genetic dysfunction of telomerase: medical genetics of telomerase Dyskeratosis congenita Aplastic anaemia Idiopathic pulmonary fibrosis Acute myeloid leukaemia TERT and TERC variations and disease predisposition Summary and perspectives Acknowledgements Telomerase is a specialized reverse transcriptase that extends and maintains the terminal ends of chromosomes, or telomeres. Since its discovery in 1985 by Nobel Laureates Elizabeth Blackburn and Carol Greider, thousands of articles have emerged detailing its significance in telomere function and cell survival. This review provides a current assessment on the importance of telomerase regulation and relates it in terms of medical genetics. In this review, we discuss the recent findings on telomerase regulation, focusing on epigenetics and non-coding RNAs regulation of telomerase, such as microRNAs and the recently discovered telomeric-repeat containing RNA transcripts. Human genetic disorders that develop due to mutations in telomerase subunits, the role of single nucleotide polymorphisms in genes encoding telomerase components and diseases as a result of telomerase regulation going awry are also discussed. Continual investigation of the complex regulation of telomerase will further our insight into the use of controlling telomerase activity in medicine.