Microbial symbionts of insects provide a range of ecological traits to their hosts that are beneficial in the context of biotic interactions. However, little is known about insect symbiont-mediated adaptation to the abiotic environment, for example, temperature and humidity. Here, we report on an ancient clade of intracellular, bacteriome-located Bacteroidetes symbionts that are associated with grain and wood pest beetles of the phylogenetically distant families Silvanidae and Bostrichidae. In the saw-toothed grain beetle Oryzaephilus surinamensis, we demonstrate that the symbionts affect cuticle thickness, melanization and hydrocarbon profile, enhancing desiccation resistance and thereby strongly improving fitness under dry conditions. Together with earlier observations on symbiont contributions to cuticle biosynthesis in weevils, our findings indicate that convergent acquisitions of bacterial mutualists represented key adaptations enabling diverse pest beetle groups to survive and proliferate under the low ambient humidity that characterizes dry grain storage facilities.

14Microbial symbionts of insects provide a range of ecological traits to their hosts that are beneficial in the 15 context of biotic interactions. However, little is known about insect symbiont-mediated adaptation to the 16 abiotic environment, e.g. temperature and humidity. Here we report on an ancient (~400 Mya) clade of 17 intracellular, bacteriome-located Bacteroidetes symbionts that are associated withgrain and wood pest 18 beetles of the phylogenetically distant families Silvanidae and Bostrichidae. In the saw-toothed grain beetle 19Oryzaephilus surinamensis, we demonstrate that the symbionts affect cuticle thickness, melanization and 20 hydrocarbon profile, enhancing desiccation resistance and thereby strongly improving fitness under dry 21 conditions. Together with earlier observations on symbiont contributions to cuticle biosynthesis in weevils, 22 our findings indicate that convergent acquisitions of bacterial mutualists represented key adaptations 23 enabling diverse pest beetle groups to survive and proliferate under the low ambient humidities that 24 characterize dry grain storage facilities. 25 26 Introduction 27

Nucleic acid accumulation in repeat expansion disease poses multiple challenges to cellular integrity. Myotonic dystrophy type 2 (DM2) results from large CCTG repeats in the CNBP gene leading to myopathy and an increased prevalence of autoimmunity. Here, we observed that DM2 patients exhibited a type-I interferon signature in blood and cultured fibroblasts. RNA repeat accumulation was prevalent in the cytosol of DM2 patient fibroblasts, facilitating repeat-associated non-AUG translation. The ensuing chronic endoplasmic reticulum (ER) stress response led to an ATF6-controlled induction of type-I IFN dependent on the cGAS/STING pathway. Recapitulating chronic ER stress in the monocytic THP-1 cell line revealed its dependence on mitochondrial DNA (mtDNA). Correspondingly, mitochondrial stress and cytosolic leakage of mtDNA was observed in DM2 patient fibroblasts. Altogether, our study demonstrates a novel mechanism by which large repeat expansions cause chronic ER and mitochondrial stress and induce a type-I interferon response that predisposes to autoimmunity. Keywords: ER stress, ATF6, Autoimmunity, type I IFN, repeat expansions

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