Impaired biogenesis of basic proteins impacts multiple hallmarks of the aging brain.

IF 2 2区生物学 Q2 EVOLUTIONARY BIOLOGY

Taxon Pub Date : 2024-01-09 DOI:10.1101/2023.07.20.549210

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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引用次数: 0

Abstract

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.

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基础蛋白质的生物生成受损会影响大脑衰老的多个特征。

衰老和神经退行性变会导致多种细胞和分子特征。在这里，我们研究了衰老对短寿命鳉鱼大脑转录组、翻译组和多层蛋白质组的影响。我们发现，衰老会导致富含碱性氨基酸的蛋白质广泛减少，这与 mRNA 的调控无关，也不是蛋白酶体活性受损所致。相反，我们发现了一连串事件，在这些事件中，异常翻译暂停导致核糖体可用性降低，从而导致蛋白质组重塑，而与转录调控无关。我们的研究发现了衰老大脑生物学中的一个脆弱点--基本 DNA/RNA 结合蛋白的生物生成。这一弱点可能代表着一个统一的原则，它将各种衰老特征联系在一起，包括基因组完整性和大分子的生物合成。一句话总结：翻译暂停重塑了衰老大脑蛋白质组，揭示了核酸蛋白生物生成过程中的弱点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Taxon 生物-进化生物学

CiteScore

4.70

自引率

8.80%

发文量

177

审稿时长

6-12 weeks

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.