Regulated expression of the lncRNA TERRA and its impact on telomere biology

Abstract

The telomere protects against genomic instability by minimizing the accelerated end resection of the genetic material, a phenomenon that results in severe chromosome instability that could favor the transformation of a cell by enabling the emergence of tumor-promoting mutations. Some mechanisms that avoid this fate, such as capping and loop formation, have been very well characterized; however, telomeric non-coding transcripts, such as long non-coding RNAs (lncRNAs), should also be considered in this context because they play roles in the organization of telomere dynamics, involving processes such as replication, degradation, extension, and heterochromatin stabilization. Although the mechanism through which the expression of telomeric transcripts regulates telomere dynamics is not yet clear, a non-coding RNA component opens the research options in telomere biology and the impact that it can have on telomere-associated diseases such as cancer.

Telomere Homeostasis: Interplay with Magnesium

“…G-wires are highly resistant to denaturation and have been reported to interfere with telomerase function [53,55,57]. In addition, some proteins appear to recognise specifically G-quadruplex structures, such as the GAR domain of the shelterin protein TRF2 [58]. …”

“…An important player in this context is TERRA, a class of long ncRNA (lncRNA) transcribed from insulated promoters within telomeric and sub-telomeric regions that largely escape heterochromatinization. This class of RNA varies considerably in length, from approximately 100 bases to 9 kilobases (kb), and contains telomeric repeats [58]. The accumulation of mutations within the sequence allows TERRA to have, at the same time, specific binding in cis to the telomere of origin and generalised activity in trans on any chromosome [67].…”

“…While the picture of TERRA’s full role inside the cell is not yet clear, evidence has been accumulating on TERRA fulfilling a variety of functions related to telomere maintenance [58,67,68]. TERRA can interact with telomeric DNA to form hybrid DNA-RNA G-quadruplexes, interact with components of the shelterin complex, and bind telomerase [58].…”

“…TERRA can interact with telomeric DNA to form hybrid DNA-RNA G-quadruplexes, interact with components of the shelterin complex, and bind telomerase [58]. TERRA is also thought to play a role in organising and expanding telomeric heterochromatin [69] and to help in telomere homeostasis.…”

Long Non-Coding RNA Signature in Cervical Cancer

“…These so-called long non-cod ing RNA (lncRNAs) have tissue specific expression pattern [2] but are less conserved than protein cod ing RNAs [3]. They are involved in almost every aspect of physiological processes, such as preservation of DNA integrity [4], telomere bio logy [5], immune cell homeostasis [6], regulation of hormone receptors [7] as well as differentiation and homeostasis of metabolic tissues [8]. The differential expression of lncRNAs in malignant tissues compared with normal tissues of the same origin has been demonstrated in several studies [3,[9][10][11][12][13][14] what implies their role in pathogenesis of different cancers.…”