Regulating translation in aging: from global to gene-specific mechanisms.

IF 6.5 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY EMBO Reports Pub Date : 2024-11-19 DOI:10.1038/s44319-024-00315-2

Mathilde Solyga, Amitabha Majumdar, Florence Besse

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Abstract

Aging is characterized by a decline in various biological functions that is associated with changes in gene expression programs. Recent transcriptome-wide integrative studies in diverse organisms and tissues have revealed a gradual uncoupling between RNA and protein levels with aging, which highlights the importance of post-transcriptional regulatory processes. Here, we provide an overview of multi-omics analyses that show the progressive uncorrelation of transcriptomes and proteomes during the course of healthy aging. We then describe the molecular changes leading to global downregulation of protein synthesis with age and review recent work dissecting the mechanisms involved in gene-specific translational regulation in complementary model organisms. These mechanisms include the recognition of regulated mRNAs by trans-acting factors such as miRNA and RNA-binding proteins, the condensation of mRNAs into repressive cytoplasmic RNP granules, and the pausing of ribosomes at specific residues. Lastly, we mention future challenges of this emerging field, possible buffering functions as well as potential links with disease.

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衰老过程中的翻译调控：从全球机制到基因特异性机制。

衰老的特征是各种生物功能的下降，这与基因表达程序的变化有关。最近在不同生物体和组织中进行的全转录组整合研究发现，随着年龄的增长，RNA 和蛋白质水平逐渐脱钩，这凸显了转录后调控过程的重要性。在这里，我们概述了多组学分析，这些分析表明转录组和蛋白质组在健康衰老过程中逐渐失去相关性。然后，我们描述了导致蛋白质合成随年龄增长而全面下调的分子变化，并回顾了最近在互补模式生物中剖析基因特异性翻译调控机制的工作。这些机制包括 miRNA 和 RNA 结合蛋白等反式作用因子识别受调控的 mRNA、将 mRNA 凝聚成抑制性细胞质 RNP 颗粒以及核糖体在特定残基处暂停。最后，我们提到了这一新兴领域未来的挑战、可能的缓冲功能以及与疾病的潜在联系。

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

EMBO Reports 生物-生化与分子生物学

CiteScore

11.20

自引率

1.30%

发文量

267

审稿时长

1 months

期刊介绍： EMBO Reports is a scientific journal that specializes in publishing research articles in the fields of molecular biology, cell biology, and developmental biology. The journal is known for its commitment to publishing high-quality, impactful research that provides novel physiological and functional insights. These insights are expected to be supported by robust evidence, with independent lines of inquiry validating the findings. The journal's scope includes both long and short-format papers, catering to different types of research contributions. It values studies that: Communicate major findings: Articles that report significant discoveries or advancements in the understanding of biological processes at the molecular, cellular, and developmental levels. Confirm important findings: Research that validates or supports existing knowledge in the field, reinforcing the reliability of previous studies. Refute prominent claims: Studies that challenge or disprove widely accepted ideas or hypotheses in the biosciences, contributing to the correction and evolution of scientific understanding. Present null data: Papers that report negative results or findings that do not support a particular hypothesis, which are crucial for the scientific process as they help to refine or redirect research efforts. EMBO Reports is dedicated to maintaining high standards of scientific rigor and integrity, ensuring that the research it publishes contributes meaningfully to the advancement of knowledge in the life sciences. By covering a broad spectrum of topics and encouraging the publication of both positive and negative results, the journal plays a vital role in promoting a comprehensive and balanced view of scientific inquiry.