Oxidative stress induces transcription of telomeric repeat-containing RNA (TERRA) by engaging PKA signaling and cytoskeleton dynamics.

Autor: Galigniana NM; Laboratory of Nuclear Architecture, Instituto de Biología y Medicina Experimental (IByME-CONICET), Ciudad Autónoma de Buenos Aires, Argentina., Charó NL; Laboratory of Nuclear Architecture, Instituto de Biología y Medicina Experimental (IByME-CONICET), Ciudad Autónoma de Buenos Aires, Argentina., Uranga R; Instituto de Investigaciones Bioquímicas de Bahía Blanca (IIBBB-CONICET), Departamento de Biología, Bioquímica y Farmacia, Universidad Nacional del Sur, Bahía Blanca, Argentina., Cabanillas AM; Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI-CONICET), Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, Argentina., Piwien-Pilipuk G; Laboratory of Nuclear Architecture, Instituto de Biología y Medicina Experimental (IByME-CONICET), Ciudad Autónoma de Buenos Aires, Argentina. Electronic address: gpiwien@conicet.gov.ar.
Jazyk: angličtina
Zdroj: Biochimica et biophysica acta. Molecular cell research [Biochim Biophys Acta Mol Cell Res] 2020 Apr; Vol. 1867 (4), pp. 118643. Date of Electronic Publication: 2020 Jan 07.
DOI: 10.1016/j.bbamcr.2020.118643
Abstrakt: Long non-coding RNAs transcribed from telomeres, known as TERRA (telomeric repeat-containing RNA), are associated with telomere and genome stability. TERRA abundance responds to different cell stresses; however, no studies have focused on oxidative stress, condition that damages biomolecules and is involved in aging and disease. Since telomeres are prone to oxidative damage leading to their dysfunction, our objective was to characterize TERRAs and the mechanisms that control their expression. TERRA increased in cells exposed to H 2 O 2 and reverted by antioxidant treatment. TERRAs are also induced in brown adipose tissue of mice exposed to cold, which raises mitochondrial ROS. In cells exposed to H 2 O 2 , ChIP showed that chromatin landscape was modified favoring telomere transcription. TERRAs interacted with HP1α/γ, proteins that were found recruited to subtelomeres. Since HP1γ interacts with the transcriptional machinery, TERRAs may stimulate their own expression by recruiting HP1γ to subtelomeres. TERRA induction reverted within 2 h after removal of H 2 O 2 from culture medium, suggesting they have protective functions. This was supported by rapid TERRA induction following a second H 2 O 2 challenge. PKA inhibitors H89 and PKI blocked TERRA increase by H 2 O 2 or IBMX+Forskolin treatment, suggesting PKA signaling regulates TERRA induction. Treatment of cells with drugs that disturb cytoskeleton integrity or growing cells on surfaces of different stiffness known to generate differential cytoskeleton tension also modified TERRA levels and sensitized cells to lower H 2 O 2 concentrations. In summary, we show that TERRAs are induced in response to oxidative stress and are regulated by PKA as well as by changes in cytoskeleton dynamics.
(Copyright © 2020 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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