Telomerase and telomeric proteins: a life beyond telomeres.

Telomerase was discovered as the enzyme deputed to telomere maintenance. In human somatic cells, its activity is virtually absent, and cells stop proliferating when telomeres fall below a critical length. In contrast, in the vast majority of tumors, telomerase is active and its activity is associated with telomere preservation and with the acquisition of an unlimited proliferative potential. Despite this well known and consolidated role of telomerase, a large body of evidence indicates that it contributes to cellular physiology independently of telomere length maintenance. Multiple roles of telomerase in cancer development have been highlighted, besides telomere lengthening, among which is gene expression regulation. More recently, the telomerase catalytic subunit has been shown to associate with an RNA molecule different from the telomerase RNA, giving rise to a complex with functions unrelated to telomere metabolism. Besides telomerase, telomeric proteins play a fundamental role in telomere maintenance. In particular, a six protein complex, named shelterin, is stably associated with telomeres and is essential for telomere metabolism. As well as for telomerase, additional roles beyond telomeres have been found for telomeric proteins, in particular for the TRF2 subunit of shelterin. In this review, we will discuss extra-telomeric functions of telomerase and TRF2 in different biological processes.