Reduced RNA turnover as a driver of cellular senescence.
Life Sci Alliance
; 4(3)2021 03.
Article
em En
| MEDLINE
| ID: mdl-33446491
ABSTRACT
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.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
RNA
/
Senescência Celular
/
Estabilidade de RNA
Limite:
Humans
Idioma:
En
Revista:
Life Sci Alliance
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
França