Human Telomerase RNA: Telomerase Component or More?

Abstract

Telomerase is a ribonucleoprotein complex that maintains the lengths of telomeres. Most studies of telomerase function have focused on the involvement of telomerase activation in the immortalization of cancer cells and cellular rejuvenation. However, some studies demonstrated that the results do not meet expectations for telomerase action in telomere maintenance. Recent results give reason to think that major telomerase components—the reverse transcriptase protein subunit and telomerase RNA—may participate in many cellular processes, including the regulation of apoptosis and autophagy, cell survival, pro-proliferative effects, regulation of gene expression, and protection against oxidative stress. However, the difficulties faced by scientist when researching telomerase component functions often reduce confidence in the minor effects observed in experiments. In this review, we focus on the analysis of the functions of telomerase components (paying more attention to the telomerase RNA component), both as a complex and as independent components, providing effects that are not associated with telomerase activity and telomere length maintenance. Despite the fact that the data on alternative roles of telomerase components look illusory, it would be wrong to completely reject the possibility of their involvement in other biological processes excluded from research/discussion. Investigations to improve the understanding of every aspect of the functioning of telomerase components will provide the basis for a more precise development of approaches to regulate cellular homeostasis, which is important for carcinogenesis and aging.

Telomere Length as a Marker of Biological Age: State-of-the-Art, Open Issues, and Future Perspectives

“…The size of critically short (“uncapped”) telomeres may be stabilized by telomerase, a reverse transcriptase enzyme that can elongate chromosome ends de novo . Two main components of human telomerase are telomerase reverse transcriptase (TERT) and telomerase RNA component (TERC) serving as a template for the telomere elongation (Rubtsova and Dontsova, 2020 ). In humans, this enzyme is known to be expressed during early in-utero development, is inactivated in most adult cells except for the germ line and embryonic stem cells and immune cells, and reactivated in the majority of cancers (Shay and Wright, 2019 ).…”

Composition and Function of Telomerase—A Polymerase Associated with the Origin of Eukaryotes

“…The human TR primary transcript is synthesized by RNA Pol II, capped on its 5 end with a monomethylguanosine (MMG) cap that is further methylated to N2, 2, 7 trimethylguanosine (TMG) cap [81][82][83], internally modified, and processed at its 3 end to generate the mature, functional TR (reviewed in [65,84]). Several structural motifs and the formation of the overall tertiary structure of TR are needed for a proper interaction with the TERT subunit (reviewed in [85]). Although TERT can bind to TR through the t/PK domain alone, additional binding with the CR4/5 domain is required [86,87].…”

“…It was demonstrated that, e.g., the TR subunit was upregulated at very early stages of tumorigenesis, whereas telomerase activity was detected in end-stage tumors [164], and that the RNA component seems to be capable of DNA damage response (DDR) regulation [165]. The TERT subunit, independently of its action on telomeres, regulates the cell-cycle, inhibits apoptosis, regulates gene expression, modulates cell signaling (e.g., Wnt/β-catenin, NF-κB pathways) and DDR, and binds to and protects mitochondrial DNA (mtDNA) (reviewed in [85,163,166]).…”

Telomere Length and Hematological Disorders: A Review

“…telomerase complex, being characterized by telomere elongation and in 90% of the cases it is due to the reactivation of telomerase enzyme (Figure 2) (12)(13)(14).…”