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Telomeric RNA (TERRA) increases in response to spaceflight and high-altitude climbing.
Al-Turki, Taghreed M; Maranon, David G; Nelson, Christopher B; Lewis, Aidan M; Luxton, Jared J; Taylor, Lynn E; Altina, Noelia; Wu, Fei; Du, Huixun; Kim, JangKeun; Damle, Namita; Overbey, Eliah; Meydan, Cem; Grigorev, Kirill; Winer, Daniel A; Furman, David; Mason, Christopher E; Bailey, Susan M.
Afiliación
  • Al-Turki TM; Department of Environmental and Radiological Health Sciences, Colorado State University, Fort Collins, CO, USA.
  • Maranon DG; Cell and Molecular Biology Program, Colorado State University, Fort Collins, CO, USA.
  • Nelson CB; Lineberger Comprehensive Cancer Center and Departments of Microbiology and Immunology, and Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.
  • Lewis AM; Department of Environmental and Radiological Health Sciences, Colorado State University, Fort Collins, CO, USA.
  • Luxton JJ; Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, CO, USA.
  • Taylor LE; Department of Environmental and Radiological Health Sciences, Colorado State University, Fort Collins, CO, USA.
  • Altina N; Cell and Molecular Biology Program, Colorado State University, Fort Collins, CO, USA.
  • Wu F; Children's Medical Research Institute, 214 Hawkesbury Road, Westmead, Sydney, NSW, 2145, Australia.
  • Du H; Department of Environmental and Radiological Health Sciences, Colorado State University, Fort Collins, CO, USA.
  • Kim J; Cell and Molecular Biology Program, Colorado State University, Fort Collins, CO, USA.
  • Damle N; Department of Environmental and Radiological Health Sciences, Colorado State University, Fort Collins, CO, USA.
  • Overbey E; Cell and Molecular Biology Program, Colorado State University, Fort Collins, CO, USA.
  • Meydan C; Department of Environmental and Radiological Health Sciences, Colorado State University, Fort Collins, CO, USA.
  • Grigorev K; Cell and Molecular Biology Program, Colorado State University, Fort Collins, CO, USA.
  • Winer DA; Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, CO, USA.
  • Furman D; Buck AI Platform, Buck Institute for Research on Aging, Novato, CA, USA.
  • Mason CE; Buck AI Platform, Buck Institute for Research on Aging, Novato, CA, USA.
  • Bailey SM; Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY, USA.
Commun Biol ; 7(1): 698, 2024 Jun 11.
Article en En | MEDLINE | ID: mdl-38862827
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 TERRAtelomeric 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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Vuelo Espacial / Telómero / Altitud Límite: Adult / Female / Humans / Male / Middle aged Idioma: En Revista: Commun Biol Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Vuelo Espacial / Telómero / Altitud Límite: Adult / Female / Humans / Male / Middle aged Idioma: En Revista: Commun Biol Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido