Impact of hydrogen peroxide (H2O2) on transcription in Jurkat T cells

ABSTRACT: Accumulation of senescent cells is an important contributor to chronic inflammation upon aging. While the transcription factors driving the inflammatory phenotype of senescent cells have been extensively studies, the triggers of the pro-inflammatory pathways are still incompletely characterized. Here, we show that cells driven into senescence by different routes share a deficiency in RNA degradation activity most correlated with reduced expression of one or several subunits of the RNA exosome. A similar deficiency was also detected in cells exposed to oxidative stress, either acute, by treatment with hydrogen peroxide, or more long-term in a mouse model for mitochondrial suffering. Reciprocally, inactivation of RNA exosome activity reduced expression of mitochondrial genes while promoting senescence markers, suggesting that the RNAs accumulating as a consequence of the reduced turnover, have a function in promoting some aspects of the senescent phenotype. Consistent with this, we show that some of the RNA species detected in senescent cells are also produced during normal activation of immune cells and contain Alu sequences known to trigger an innate immune response. We propose that these RNA species participate in driving and maintaining the permanent inflammatory state characteristic of cellular senescence.

ORGANISM(S): Homo sapiens

PROVIDER: GSE138290 | GEO | 2021/06/01

REPOSITORIES: GEO