Cell adaptation to aneuploidy by the environmental stress response dampens induction of the cytosolic unfolded-protein response.

Aneuploid yeast cells are in a chronic state of proteotoxicity, yet do not constitutively induce the cytosolic unfolded protein response, or heat shock response (HSR) by heat shock factor 1 (Hsf1). Here, we demonstrate that an active environmental stress response (ESR), a hallmark of aneuploidy across different models, suppresses Hsf1 induction in models of single-chromosome gain. Furthermore, engineered activation of the ESR in the absence of stress was sufficient to suppress Hsf1 activation in euploid cells by subsequent heat shock while increasing thermotolerance and blocking formation of heat-induced protein aggregates.

The host Integrator complex acts in transcription-independent maturation of herpesvirus microRNA 3' ends.

Herpesvirus saimiri (HVS) is an oncogenic γ-herpesvirus that produces microRNAs (miRNAs) by cotranscription of precursor miRNA (pre-miRNA) hairpins immediately downstream from viral small nuclear RNAs (snRNA). The host cell Integrator complex, which recognizes the snRNA 3' end processing signal (3' box), generates the 5' ends of HVS pre-miRNA hairpins. Here, we identify a novel 3' box-like sequence (miRNA 3' box) downstream from HVS pre-miRNAs that is essential for miRNA biogenesis.

Otopetrin 1 protects mice from obesity-associated metabolic dysfunction through attenuating adipose tissue inflammation.

Chronic low-grade inflammation is emerging as a pathogenic link between obesity and metabolic disease. Persistent immune activation in white adipose tissue (WAT) impairs insulin sensitivity and systemic metabolism, in part, through the actions of proinflammatory cytokines. Whether obesity engages an adaptive mechanism to counteract chronic inflammation in adipose tissues has not been elucidated.