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Reduced RNA turnover as a driver of cellular senescence

Abstract : Accumulation of senescent cells is an important contributor to chronic inflammation upon aging.Whilecytoplasmic DNA was shown to drivethe inflammatory phenotype of senescent cells, an equivalent role for RNA has never been explored.Here, we show that cellular senescence correlates with reduced expression ofRNA exosomesubunitsand coincident accumulation of promoter RNAs and immature RNA transcripts.Forced accumulation of these RNAs by inactivation of the Exosc3exosome subunit induces expression of senescence markersand reduced mitochondrial gene expression. Reciprocally, mitochondrial suffering and oxidative stress results in reduced RNA decay, suggestive of a feedback loop betweenRNA decay and mitochondrial activity. As severalof the accumulating RNAsare also produced during normal activation of immune cells and contain Alu sequences known to trigger an innate immune response, we propose that stabilizing immature and unstable RNAs participate in driving andmaintaining the permanent inflammatory state characteristic of cellular senescence.
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Contributor : Eric Batsche Connect in order to contact the contributor
Submitted on : Monday, October 21, 2019 - 6:34:42 PM
Last modification on : Friday, December 3, 2021 - 11:42:37 AM


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Nowsheen Mullani, Mickaël Costallat, Eric Batsche, Yevheniia Porozan, Ida Guerrera, et al.. Reduced RNA turnover as a driver of cellular senescence. 2019. ⟨hal-02324027v1⟩



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