Current Perspectives of Telomerase Structure and Function in Eukaryotes with Emerging Views on Telomerase in Human Parasites

Abstract

Replicative capacity of a cell is strongly correlated with telomere length regulation. Aberrant lengthening or reduction in the length of telomeres can lead to health anomalies, such as cancer or premature aging. Telomerase is a master regulator for maintaining replicative potential in most eukaryotic cells. It does so by controlling telomere length at chromosome ends. Akin to cancer cells, most single-cell eukaryotic pathogens are highly proliferative and require persistent telomerase activity to maintain constant length of telomere and propagation within their host. Although telomerase is key to unlimited cellular proliferation in both cases, not much was known about the role of telomerase in human parasites (malaria, Trypanosoma, etc.) until recently. Since telomerase regulation is mediated via its own structural components, interactions with catalytic reverse transcriptase and several factors that can recruit and assemble telomerase to telomeres in a cell cycle-dependent manner, we compare and discuss here recent findings in telomerase biology in cancer, aging and parasitic diseases to give a broader perspective of telomerase function in human diseases.

Improving a fish intestinal barrier model by combining two rainbow trout cell lines: epithelial RTgutGC and fibroblastic RTgutF

“…In support of this observation, cells express slightly rising levels of telomerase over passages (Fig. 2c), an enzyme known to extend cell longevity by extending the chromosome termini, which are otherwise shortened with each cell cycle (Dey and Chakrabarti 2018). In some species, including rainbow trout, telomerase activity is not limited to stem cells, but was detected in all somatic cells (Klapper et al 1998).…”

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

“…The presence of TERT was detected in early branching eukaryotes [53,54]. It was proposed that telomerase originated as an ancient reverse transcriptase (RT) that internalized a primitive template-bearing RNA during early eukaryotic evolution, and later evolved into modern telomerase ribonucleoproteins (RNPs) with various indispensable and stably TR-associated components [55,56]. In accordance with this notion, the TERT subunit has the ability to bind not exclusively the RNA molecule that provides the template sequence for DNA synthesis (TR), but also various non-telomeric sequences [57,58].…”

“…The conserved RT motifs between TERT and other RTs indicates that the TERT protein is closely related to RTs from the group of Penelope-like Elements (PLEs) and non-long-terminal-repeat (non-LTR) retrotransposons [55]. PLEs have an RT that lacks endonuclease activity, and it is plausible that ancient retrotransposons similar to these terminal PLEs might be the progenitors of TERT proteins [56].…”

Possible Involvement of Hsp90 in the Regulation of Telomere Length and Telomerase Activity During the Leishmania amazonensis Developmental Cycle and Population Proliferation

“…Also, few human vaccines in clinical trials demonstrate the urgency of finding new anti-parasite therapies that are less toxic and more active (Hotez et al, 2016;Moafi et al, 2019;World Health Organization [WHO], 2020). Thus, an increasing interest in studying telomeres as drug design targets has emerged (Olaussen et al, 2006;Chen et al, 2009;Sekaran et al, 2014;Dey and Chakrabarti, 2018). Telomeres are protein-DNA complexes that protect chromosome ends from degradation and fusion (Giardini et al, 2014).…”