探索核糖体密码:揭示致癌基因调控的新维度

Yuen Gao
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摘要

分子生物学的中心教条传统上认为核糖体是统一的实体,以机械精度将mRNA翻译成蛋白质。最近的研究结果挑战了这一观点,揭示了细胞内意想不到的核糖体异质性,从而提出了一种多样化蛋白质合成的新机制。这一概念与“组蛋白密码”假说相似,导致了“核糖体密码”的命题,该命题表明核糖体蛋白化学计量、类似物和修饰的变化可能优先翻译某些mRNA群体。然而,核糖体异质性在癌症发病机制中的作用仍然是一个有争议的话题。有证据表明,核糖体组成、结构和活性的改变可能影响异常的蛋白质合成,从而促进肿瘤的发生。增强的核糖体生物发生、蛋白质合成和肿瘤生长之间的相关性,以及在癌症核糖体中观察到的修饰,都支持了这一点。研究核糖体异质性的细微差别,其对翻译偏差的影响,以及对肿瘤生物学的影响,可以显著加深我们对癌症分子景观的理解,潜在地揭示新的治疗靶点。
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Exploring Ribosome Code: Unveiling A Novel Dimension of Gene Regulation in Carcinogenesis
The central dogma of molecular biology has traditionally viewed ribosomes as uniform entities translating mRNA into proteins with mechanical precision. Recent findings challenge this perspective, revealing unexpected ribosome heterogeneity within cells, thus proposing a novel mechanism for diversifying protein synthesis. This concept parallels the “histone code” hypothesis, leading to the proposition of a “ribosome code” that suggests variations in ribosomal protein stoichiometry, paralogs, and modifications may preferentially translate certain mRNA populations. The role of ribosome heterogeneity in cancer pathogenesis, however, remains a subject of debate. Evidence suggests that alterations in ribosome composition, structure, and activity could influence abnormal protein synthesis, thus contributing to tumorigenesis. This is supported by the correlation between enhanced ribosome biogenesis, protein synthesis, and tumor growth, as well as the observed modifications in cancer ribosomes. Examining the nuances of ribosome heterogeneity, its influence on translational biases, and implications for tumor biology could significantly deepen our understanding of cancer’s molecular landscape, potentially unveiling novel therapeutic targets.
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