TY - JOUR T1 - Reduced RNA turnover as a driver of cellular senescence JF - Life Science Alliance JO - Life Sci. Alliance DO - 10.26508/lsa.202000809 VL - 4 IS - 3 SP - e202000809 AU - Nowsheen Mullani AU - Yevheniia Porozhan AU - Adèle Mangelinck AU - Christophe Rachez AU - Mickael Costallat AU - Eric Batsché AU - Michele Goodhardt AU - Giovanni Cenci AU - Carl Mann AU - Christian Muchardt Y1 - 2021/03/01 UR - https://www.life-science-alliance.org/content/4/3/e202000809.abstract N2 - Accumulation of senescent cells is an important contributor to chronic inflammation upon aging. The inflammatory phenotype of senescent cells was previously shown to be driven by cytoplasmic DNA. Here, we propose that cytoplasmic double-stranded RNA has a similar effect. We find that several cell types driven into senescence by different routes share an accumulation of long promoter RNAs and 3′ gene extensions rich in retrotransposon sequences. Accordingly, these cells display increased expression of genes involved in response to double stranded RNA of viral origin downstream of the interferon pathway. The RNA accumulation is associated with evidence of reduced RNA turnover, including in some cases, reduced expression of RNA exosome subunits. Reciprocally, depletion of RNA exosome subunit EXOSC3 accelerated expression of multiple senescence markers. A senescence-like RNA accumulation was also observed in cells exposed to oxidative stress, an important trigger of cellular senescence. Altogether, we propose that in a subset of senescent cells, repeat-containing transcripts stabilized by oxidative stress or reduced RNA exosome activity participate in driving and maintaining the permanent inflammatory state characterizing cellular senescence. ER -