.
P A Y W A L L E D S O U R C E : Aging Research Reviews
• Telomeric non-coding RNAs arise as prospective biomarkers of ageing.
• A direct role of TERRA and telomeric damage-induced long non-coding RNAs in telomere biology and ageing.
• Telomeric non-coding RNAs accumulate in premature ageing conditions and fuel DNA damage responses at telomeres.
• Telomere-sequenced Antisense Oligonucleotides improve the detrimental phenotypes of human premature ageing.
Abstract
Telomeres, the ends of eukaryotic chromosomes, play a central role in the control of cellular senescence and organismal ageing and need to be protected in order to avoid being recognised as damaged DNA and activate DNA damage response pathways. Dysfunctional telomeres arise from critically short telomeres or altered telomere structures, which ultimately lead to replicative cellular senescence and chromosome instability: both hallmarks of ageing. The observation that telomeres are transcribed led to the discovery that telomeric transcripts play important roles in chromosome end protection and genome stability maintenance.
Recent evidence indicates that particular long non-coding (nc)RNAs transcribed at telomeres, namely TElomeric Repeat-containing RNA (TERRA) and telomeric damage-induced long ncRNAs (tdilncRNA), play key roles in age-related pathways by actively orchestrating the mechanisms known to regulate telomere length, chromosome end protection and DNA damage signalling. Here, we provide a comprehensive overview of the telomere transcriptome, outlining how it functions as a regulatory platform with essential functions in safeguarding telomere integrity and stability.
We next review emerging antisense oligonucleotides therapeutic strategies that target telomeric ncRNAs and discuss their potential for ameliorating ageing and age-related diseases. Altogether, this review provides insights on the biological relevance of telomere transcription mechanisms in human ageing physiology and pathology.
OUTLINE:
1. Introduction
1.1. Telomere dynamics in senescence
1.2. Telomere transcription dynamics
1.3. TERRA in senescence and ageing
1.4. Functional characterization of tdilncRNAs and tDDRNAs in ageing
2. Conclusions and future perspectives
Declaration of Competing Interest
Acknowledgments
References
.
