Domenico Di Fraia, Antonio Marino, Jae Ho Lee, Erika Kelmer Sacramento, Mario Baumgart, Sara Bagnoli, Pedro Tomaz da Silva, Amit Kumar Sahu, Giacomo Siano, Max Tiessen, Eva Terzibasi-Tozzini, Julien Gagneur, Judith Frydman, Alessandro Cellerino, Alessandro Ori
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Impaired biogenesis of basic proteins impacts multiple hallmarks of the aging brain.
Aging and neurodegeneration entail diverse cellular and molecular hallmarks. Here, we studied the effects of aging on the transcriptome, translatome, and multiple layers of the proteome in the brain of a short-lived killifish. We reveal that aging causes widespread reduction of proteins enriched in basic amino acids that is independent of mRNA regulation, and it is not due to impaired proteasome activity. Instead, we identify a cascade of events where aberrant translation pausing leads to reduced ribosome availability resulting in proteome remodeling independently of transcriptional regulation. Our research uncovers a vulnerable point in the aging brain's biology - the biogenesis of basic DNA/RNA binding proteins. This vulnerability may represent a unifying principle that connects various aging hallmarks, encompassing genome integrity and the biosynthesis of macromolecules.
期刊介绍：
TAXON is the bi-monthly journal of the International Association for Plant Taxonomy and is devoted to systematic and evolutionary biology with emphasis on plants and fungi. It is published bimonthly by the International Bureau for Plant Taxonomy and Nomenclature, c/o Institute of Botany, Slovak Academy of Sciences, Dúbravská cesta 9, SK-845 23 Bratislava, SLOVAKIA. Details of page charges are given in the Guidelines for authors. Papers will be reviewed by at least two specialists.
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