TERRA long noncoding RNA: At the interphase of telomere damage, rescue and signaling.
Abstract
TERRA long noncoding RNAs play key roles in telomere function and maintenance. They can orchestrate telomeric chromatin remodeling, regulate telomere maintenance by telomerase and homology-directed repair, and they participate in the telomeric DNA damage response. TERRA associates with chromosome ends through base-pairing forming R-loops, which are mediated by the RAD51 DNA recombinase and its partner RAD51AP1. Telomeric R-loops interfere with replication fork progression, stimulating a switch of telomere maintenance from semiconservative DNA replication to homology-directed repair (HDR). The latter mechanism is exploited by a subset of cancer cells that lack telomerase, referred to as ALT. In addition, TERRA stimulates HDR at short telomeres during aging, delaying cellular senescence. During carcinogenesis, when cells with eroded telomeres enter replicative crisis, TERRA acts as a signaling molecule to mediate autophagic cell death.
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Research summary
The paper discusses the role of TERRA long noncoding RNAs in telomere maintenance and their implications in cellular senescence and cancer, which are closely related to aging processes. While it provides solid insights into telomere biology and its connection to aging, the findings are more incremental rather than groundbreaking. The research contributes to understanding mechanisms that could influence longevity but does not directly address root causes of aging or propose significant interventions for lifespan extension.
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