Transcriptional regulation of telomeric non-coding RNA: implications on telomere biology, replicative senescence and cancer

Abstract

Telomeres, protective nucleoprotein structures located at the ends of eukaryotic chromosomes and until recently regarded as transcriptionally silent, are now known to be transcribed into non-coding RNA molecules called TERRA. The function(s) of TERRA in telomere metabolism is now the subject of intense study given the implications these may have on fundamental biological processes such as aging and cancer. Here is an overview of what is currently known in the novel field of telomere transcription, with regard to the evidence on the possible role of TERRA in telomeric heterochromatin formation, in the epigenetic protection of telomeres from DNA repair mechanisms, and in the regulation of telomerase activity. The implications of TERRA transcriptional regulation on telomerase activity in cancer cells and on the perception of telomere length and control of replicative senescence in cells devoid of telomere maintenance mechanisms will be discussed.