IBYME   02675
INSTITUTO DE BIOLOGIA Y MEDICINA EXPERIMENTAL
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Nuclear induction of telomeric repeat-containing RNA depends on microtubule stability under oxidative stress condictions
Autor/es:
CABANILLAS A M,; CHARÓ N L,; GALIGNIANA N. M.,; PIWIEN-PILIPUK G.
Lugar:
Buenos Aires
Reunión:
Congreso; LXI Reunión científica anual. Sociedad Argentina de Investigación Clínica (SAIC); 2016
Resumen:
Telomeres are nucleoprotein complexes at the end of linearchromosomes essential for chromosome stability, and they canbe transcribed in response to developmental changes and cellularstress conditions. These transcripts are known as telomericrepeat-containing RNA (TERRA). Increasing oxidative stress andinflammation enhance the process of erosion of telomeres witheach cycle of replication. In fact, the G-rich telomeric sequenceis more susceptible to acute oxidative damage, compared withgenomic DNA. However, little is known about how this affectsTERRA levels. Since oxidative stress is known to disrupt cytoskeletonintegrity and mechanical cues are important regulatorsof transcriptional programs, our objective was to characterizeTERRA levels using different oxidizing agents and to evaluatethe possible role of microtubules in this process. We previouslyfound that human embryonic kidney HEK-293T cells undergoinduction of TERRAs after 4h treatment with H2O2, sodium arseniteor buthionine-sulfoximine, which is prevented by antioxidanttreatment with N-acetyl-L-cysteine. In the present study, we showthat TERRA induction is mimicked by microtubule disruption usingcolcemid. Interestingly, microtubule stabilization using taxol alsoresulted in TERRA induction, suggesting that a delicate mechanotransductionmechanism is involved in TERRA regulation. Cellfractionation experiments showed that TERRAs localize in bothnuclear and cytosolic compartments, contrary to classical belief.Nevertheless, TERRA induction was only observed in the nuclearfraction, implying that only the nucleus seems to harbor the ne wlytranscribed TERRAs in response to H2O2 treatment. These resultsindicate that the nuclear functions of TERRAs may be essentialin the response of HEK-293T cells to oxidative stress caused byH2O2 exposure, possibly in order to contribute to telomere integrityand, hence, genome stability.