Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are the two common neurodegenerative diseases that have been associated with the GGGGCC·GGCCCC repeat RNA expansion in a noncoding region of C9orf72. It has been previously reported that unconventional repeat-associated non-ATG (RAN) translation of GGGGCC·GGCCCC repeats produces five types of dipeptide-repeat proteins (referred to as RAN proteins): poly-glycine-alanine (GA), poly-glycine-proline (GP), poly-glycine-arginine (GR), poly-proline-arginine (PR) and poly-proline-alanine (PA). Although protein aggregates of RAN proteins have been found in patients, it is unclear whether RAN protein aggregation induces neurotoxicity. In the present study, we aimed to understand the biological properties of all five types of RAN proteins. Surprisingly, our results showed that none of these RAN proteins was aggregate-prone in our cellular model and that the turnover of these RAN proteins was not affected by the ubiquitin-proteasome system or autophagy. Moreover, poly-GR and poly-PR, but not poly-GA, poly-GP or poly-PA, localized to the nucleolus and induced the translocation of the key nucleolar component nucleophosmin, leading to nucleolar stress and cell death. This poly-GR- and poly-PR-mediated defect in nucleolar function was associated with the suppression of ribosomal RNA synthesis and the impairment of stress granule formation. Taken together, the results of the present study suggest a simple model of the molecular mechanisms underlying RAN translation-mediated cytotoxicity in C9orf72-linked ALS/FTD in which nucleolar stress, but not protein aggregation, is the primary contributor to C9orf72-linked neurodegeneration.

Abstract• Mycorrhizal fungi and hydrogels (water-absorbing polymers) can improve water availability for trees. The combination of both factors for plant performance under water limitation has not yet been studied.• To investigate the influence of the ectomycorrhizal fungus Paxillus involutus, hydrogel and the combination of both factors, a drought-sensitive poplar, Populus euphratica, was examined in this study.• After 16 weeks of inoculation, no ectomycorrhizas were found. Nevertheless, P. involutusinoculated poplars displayed increased concentrations of soluble sugars and osmolality, leading to an improved water status. Growth was diminished compared with non-inoculated P. euphratica. The presence of hydrogels in the rooting medium resulted in increased biomass and higher plant water content and decreased the osmolality of plant tissues. Drought markedly decreased water contents in rooting medium and plants, and leaf chlorophyll fluorescence, and stimulated the root growth, concentrations of soluble sugars and osmolality in plants. Under drought conditions, P. euphratica exhibited osmoregulation by accumulation of low-molecular-weight carbohydrates.• These data indicate that adding hydrogels to soils may improve the plant performance. The reasons for improved osmoregulation by fungi and hydrogels were probably related to their stimulating influence on the formation of soluble carbohydrates under drought conditions. Mots-clés :sécheresse / hydrogel / champignon mycorhizien / peuplier / hydrates de carbone Résumé -Le champignon ectomycorhizien Paxillus involutus et les hydrogels influencent les performances de Populus euphratica en condition de stress hydrique.• Les champignons mycorhiziens et les hydrogels (polymères absorbant l'eau) peuvent améliorer la disponibilité de l'eau pour les arbres. La combinaison des deux facteurs pour améliorer la performance des plants en conditions de limitation d'eau n'a pas encore été étudiée.• Pour étudier l'influence d'un champignon ectomycorhizien Paxillus involutus, des hydrogels et la combinaison des deux facteurs, un peuplier sensible à la sécheresse, Populus euphratica, a été étudié dans ce travail.• Après 16 semaines d'inoculation, aucune ectomycorhize n'a été trouvée. Néanmoins, l'inoculation de P. involutus aux peupliers a provoqué une augmentation des concentrations de sucres solubles et de l'osmolalité conduisant à une amélioration du statut hydrique. La croissance a été diminuée par rapport à des individus non inoculés. La présence d'hydrogels dans l'enracinement a entraîné une augmentation de la biomasse et une teneur supérieure en eau des plants et une diminution de l'osmolalité des tissus des plants. La sécheresse a diminué sensiblement le contenu en eau des racines, des plants ainsi que la fluorescence de la chlorophylle des feuilles, et stimulé la croissance des racines, les concentrations de sucres solubles et l'osmolalité chez les plants. En condition de sécheresse, P. euphratica a présenté une osmorégulation par accumulation d'hydrates de carbone de faible ...