logo
ResearchBunny Logo
Telomeric RNA (TERRA) increases in response to spaceflight and high-altitude climbing

Medicine and Health

Telomeric RNA (TERRA) increases in response to spaceflight and high-altitude climbing

T. M. Al-turki, D. G. Maranon, et al.

This groundbreaking research conducted by Taghreed M. Al-Turki, David G. Maranon, and colleagues reveals how telomeric RNA, or TERRA, responds to radiation-induced DNA damage. With implications for aging and ALT-positive tumors, the study shows TERRA's crucial role in telomere stability across astronauts, climbers, and cellular models, suggesting new therapeutic strategies.

00:00
00:00
Playback language: English
Abstract
Telomeres are repetitive nucleoprotein complexes at chromosomal termini essential for maintaining genome stability. Telomeric RNA, or TERRA, is a previously presumed long noncoding RNA of heterogeneous lengths that contributes to end-capping structure and function, and facilitates telomeric recombination in tumors that maintain telomere length via the telomerase-independent Alternative Lengthening of Telomeres (ALT) pathway. Here, we investigated TERRA in the radiation-induced DNA damage response (DDR) across astronauts, high-altitude climbers, healthy donors, and cellular models. Similar to astronauts in the space radiation environment and climbers of Mt. Everest, in vitro radiation exposure prompted increased transcription of TERRA, while simulated microgravity did not. Data suggest a specific TERRA DDR to telomeric double-strand breaks (DSBs), and provide direct demonstration of hybridized TERRA at telomere-specific DSB sites, indicative of protective TERRA:telomeric DNA hybrid formation. Targeted telomeric DSBs also resulted in accumulation of TERRA foci in G2-phase, supportive of TERRA's role in facilitating recombination-mediated telomere elongation. Results have important implications for scenarios involving persistent telomeric DNA damage, such as those associated with chronic oxidative stress (e.g., aging, systemic inflammation, environmental and occupational radiation exposures), which can trigger transient ALT in normal human cells, as well as for targeting TERRA as a therapeutic strategy against ALT-positive tumors.
Publisher
Communications Biology
Published On
Jun 11, 2024
Authors
Taghreed M. Al-Turki, David G. Maranon, Christopher B. Nelson, Aidan M. Lewis, Jared J. Luxton, Lynn E. Taylor, Noelia Altina, Fei Wu, Huixun Du, JangKeun Kim, Namita Damle, Eliah Overbey, Cem Meydan, Kirill Grigorev, Daniel A. Winer, David Furman, Christopher E. Mason, Susan M. Bailey
Tags
telomeres
TERRA
DNA damage response
long noncoding RNA
telomere length
radiation exposure
ALT pathway
Listen, Learn & Level Up
Over 10,000 hours of research content in 25+ fields, available in 12+ languages.
No more digging through PDFs, just hit play and absorb the world's latest research in your language, on your time.
listen to research audio papers with researchbunny