There is a fundamental gap in understanding the consequences of tau–ribosome interactions. Tau oligomers and filaments hinder protein synthesis in vitro, and they associate strongly with ribosomes in vivo. Here, we investigated the consequences of tau interactions with ribosomes in transgenic mice, in cells, and in human brain tissues to identify tau as a direct modulator of ribosomal selectivity. First, we performed microarrays and nascent proteomics to measure changes in protein synthesis. Using regulatable rTg4510 tau transgenic mice, we determined that tau expression differentially shifts both the transcriptome and the nascent proteome, and that the synthesis of ribosomal proteins is reversibly dependent on tau levels. We further extended these results to human brains and found that tau pathologically interacts with ribosomal protein S6 (rpS6 or S6), a crucial regulator of translation. Consequently, protein synthesis under translational control of rpS6 was reduced under tauopathic conditions in Alzheimer’s disease brains. Our data establish tau as a driver of RNA translation selectivity. Moreover, since regulation of protein synthesis is critical for learning and memory, aberrant tau–ribosome interactions in disease could explain the linkage between tauopathies and cognitive impairment.Electronic supplementary materialThe online version of this article (10.1007/s00401-019-01970-9) contains supplementary material, which is available to authorized users.
La participación creciente de las inversiones en el activo del sistema financiero ha generado un mayor interés tanto en la medición como en el manejo del riesgo de mercado (RM) asociado al portafolio del Libro de Tesorería 1 , por parte de las entidades y de los reguladores. Un primer paso en esa dirección lo dio la Superintendencia Bancaria de Colombia 2 (SBC) en enero de 2002, con la implementación de los requerimientos de capital por concepto de RM. Sin embargo, recientemente esta norma ha estado sujeta a un número importante de cuestionamientos relacionados, sobre todo, con la idoneidad de la metodología utilizada para medir y cubrir apropiadamente la exposición.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.