Telomere Lengthening and Other Functions of Telomerase

Abstract

Telomerase is an enzyme that maintains the length of the telomere. The telomere length specifies the number of divisions a cell can undergo before it finally dies (i.e. the proliferative potential of cells). For example, telomerase is activated in embryonic cell lines and the telomere length is maintained at a constant level; therefore, these cells have an unlimited fission potential. Stem cells are characterized by a lower telomerase activity, which enables only partial compensation for the shortening of telomeres. Somatic cells are usually characterized by the absence of telomerase activity. Telomere shortening leads to the attainment of the Hayflick limit, the transition of cells to a state of senescence. The cells subsequently enter a state of crisis, accompanied by massive cell death. The surviving cells become cancer cells, which are capable both of dividing indefinitely and maintaining telomere length (usually with the aid of telomerase). Telomerase is a reverse transcriptase. It consists of two major components: telomerase RNA (TER) and reverse transcriptase (TERT). TER is a non-coding RNA, and it contains the region which serves as a template for telomere synthesis. An increasing number of articles focussing on the alternative functions of telomerase components have recently started appearing. The present review summarizes data on the structure, biogenesis, and functions of telomerase.

Telomere attrition: metabolic regulation and signalling function?

“…For example, telomerase is active in all tissues during development, while in adults, it is present only in mitotic tissues and stem cells (at least in humans), but its activity can vary greatly with life-history stage, tissue type and across species [117][118][119]. Telomerase is quite conserved and present in almost all organisms ranging from yeast to humans [10,70,120]. TL-lengthening via mechanisms other than telomerase have also been described in somatic cells [121].…”

“…Since telomerase also has functions that are unrelated to TL maintenance, e.g. to protect mitochondria from oxidative stress [70,71], at present there is no conclusive evidence that GCs shorten TLs by suppressing telomerase. However, as outlined above, GCs interact intimately with metabolic processes and are typically upregulated during times of high energy need to mobilize internal resources, often at the deficit of other processes that also require these resources as fuel.…”

Telomere-Related Disorders in Fetal Membranes Associated With Birth and Adverse Pregnancy Outcomes

“…Stem cell compartments and embryonic stem cells present telomerase activity; this is a ribonucleoprotein complex, composed of telomerase reverse transcriptase (TERT) and rRNA telomerase component (TERC) subunits and serves as a template for the addition of telomeric repeats to chromosome ends. However, TERT expression and telomerase activity are often very low or undetectable in somatic cells, which explain, in part, the limited capacity of somatic cells to replicate ( Rubtsova et al, 2012 ). Other pathways, such as the alternative lengthening of telomeres (ALT), have been reported in cancer cells ( De Vitis et al, 2018 ).…”

Mesenchymal Stem Cells Secretory Responses: Senescence Messaging Secretome and Immunomodulation Perspective

“…However, new data indicate that replicative senescence can also be triggered in human MSC (Wang et al, 2011 ) and a number of rodent cells prepared from laboratory animals without detectable telomere shortening (Ohtani and Hara, 2013 ). The appropriate length of the telomeres is maintained by a specialized enzyme, telomerase (Rubtsova et al, 2012 ). However, in striking contrast to somatic cells, this enzyme is expressed in human germ-line cells and adult stem cells.…”