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性与基础 mRNA 合成机制。

Sex and the basal mRNA synthesis machinery.

机构信息

Rutgers-New Jersey Medical School (NJMS), Department of Microbiology, Biochemistry, and Molecular Genetics, Newark, New Jersey, USA.

出版信息

Wiley Interdiscip Rev RNA. 2023 May-Jun;14(3):e1765. doi: 10.1002/wrna.1765. Epub 2022 Oct 4.

Abstract

Evolution and change generated an incredible diversity of organisms on this earth. Yet, some processes are so central to life that change is strongly selected against. Synthesis of the eukaryotic messenger RNA is one example. The assemblies that carry out transcription and processing (capping, polyadenylation, and splicing) are so conserved that most genes have recognizable orthologs in yeast and humans. Naturally, most would conclude transcription and processing are identical in both sexes. However, this is an assumption. Men and women vastly differ in their physiologies. The incidence of pathologies, symptom presentation, disease outcome, and therapeutic response in each sex vary enormously. Despite the harm ignorance causes women, biological research has been historically carried out without regard to sex. The male mouse was the default mammal. A cultured cell's sex was considered irrelevant. Attempts to fill this knowledge gap have revealed molecular dissimilarities. For example, the earliest embryonic male and female transcriptomes differ long before fetal sex hormones appear. We used public data to challenge the assumption of sameness by reviewing reports of sex-biased gene expression and gene targeting. We focused on 120 genes encoding nonregulatory proteins involved in mRNA synthesis. Remarkably, genes with recognizable orthologs in yeast and thus LEAST likely to differ, did differ between the sexes. The rapidly growing public databases can be used to compare the expression of any gene in male and female tissues. Appreciating the principles that drive sex differences will enrich our understanding of RNA biology in all humans-men and women. This article is categorized under: RNA in Disease and Development > RNA in Development RNA Evolution and Genomics > Computational Analyses of RNA.

摘要

进化和变化在地球上产生了令人难以置信的生物多样性。然而,有些过程对生命至关重要,以至于变化受到强烈的选择。真核生物信使 RNA 的合成就是一个例子。执行转录和加工(加帽、多聚腺苷酸化和剪接)的复合物是如此保守,以至于大多数基因在酵母和人类中都有可识别的同源物。自然而然,大多数人会得出结论,转录和加工在两性中是相同的。然而,这只是一种假设。男性和女性在生理上有很大的不同。每种性别的病理发生率、症状表现、疾病结果和治疗反应差异巨大。尽管对女性的无知造成了伤害,但生物学研究在历史上一直没有考虑到性别。雄性小鼠是默认的哺乳动物。培养细胞的性别被认为是无关紧要的。试图填补这一知识空白的尝试揭示了分子差异。例如,最早的胚胎雄性和雌性转录组在胎儿性激素出现之前就存在差异。我们使用公共数据通过审查性别偏向基因表达和基因靶向的报告来挑战相同的假设。我们专注于编码非调节蛋白的 120 个基因,这些蛋白参与 mRNA 合成。值得注意的是,在酵母中有可识别的同源物,因此不太可能有差异的基因,在两性之间确实存在差异。快速增长的公共数据库可用于比较男性和女性组织中任何基因的表达。了解驱动性别差异的原则将丰富我们对所有人类(男性和女性)中 RNA 生物学的理解。本文属于以下类别:RNA 在疾病与发育 > RNA 在发育中 RNA 进化与基因组学 > RNA 的计算分析。

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