哺乳动物细胞中编码RNA到RNA信息传递的蛋白质:RNA依赖性mRNA扩增的原理。

Vladimir Volloch
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引用次数: 0

摘要

编码遗传信息的蛋白质从DNA到RNA再到蛋白质的转移,这一过程被正式称为“分子生物学的中心法则”,自成立以来经历了重大的进化。对其进行了修改,以说明从RNA到DNA的信息流、逆转录以及从RNA到RNA的信息传递,即RNA依赖性RNA合成。这些可能导致蛋白质产生的过程最初仅在病毒系统中被描述,尽管在哺乳动物细胞中存在RNA依赖性RNA聚合酶活性,并发现RNA依赖性核糖核酸合成,但其功能被认为仅限于调节。然而,最近在几种哺乳动物系统中用多种信使核糖核酸获得的结果强烈表明,在哺乳动物细胞中发生了编码蛋白质的核糖核酸到核糖核酸的信息转移。它可以导致快速产生大量的特异性蛋白质,这在细胞终末分化和细胞外基质分子的细胞沉积过程中可以看到。该过程的故障可能涉及与该机制正常产生的蛋白质缺乏或蛋白质或其C末端片段的异常丰度相关的病理学。它似乎是某些类型的家族性地中海贫血的原因,并可能是散发性阿尔茨海默病中β淀粉样蛋白过度产生的原因。本文的目的是系统化目前对这一途径的认识和理解。概述的框架介绍了信使核糖核酸扩增的意外特征,如其产生基因组中非连续编码的多肽的能力、第二层、生理上发生的细胞内聚合酶链式反应、iPCR、“二层悖论”和RNA“暗物质”。RNA依赖性信使核糖核酸扩增代表了哺乳动物细胞中编码信息传递的基因组蛋白质的一种新模式。它的潜在生理影响是巨大的,它似乎与多种病理有关,它的理解为治疗干预开辟了新的场所,它提出了强大的新生物工程方法,它的进一步严格研究是非常有必要的。
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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Protein-Encoding RNA-to-RNA Information Transfer in Mammalian Cells: Principles of RNA-Dependent mRNA Amplification.

The transfer of protein-encoding genetic information from DNA to RNA to protein, a process formalized as the "Central Dogma of Molecular Biology", has undergone a significant evolution since its inception. It was amended to account for the information flow from RNA to DNA, the reverse transcription, and for the information transfer from RNA to RNA, the RNA-dependent RNA synthesis. These processes, both potentially leading to protein production, were initially described only in viral systems, and although RNA-dependent RNA polymerase activity was shown to be present, and RNA-dependent RNA synthesis found to occur, in mammalian cells, its function was presumed to be restricted to regulatory. However, recent results, obtained with multiple mRNA species in several mammalian systems, strongly indicate the occurrence of protein-encoding RNA to RNA information transfer in mammalian cells. It can result in the rapid production of the extraordinary quantities of specific proteins as was seen in cases of terminal cellular differentiation and during cellular deposition of extracellular matrix molecules. A malfunction of this process may be involved in pathologies associated either with the deficiency of a protein normally produced by this mechanism or with the abnormal abundance of a protein or of its C-terminal fragment. It seems to be responsible for some types of familial thalassemia and may underlie the overproduction of beta amyloid in sporadic Alzheimer's disease. The aim of the present article is to systematize the current knowledge and understanding of this pathway. The outlined framework introduces unexpected features of the mRNA amplification such as its ability to generate polypeptides non-contiguously encoded in the genome, its second Tier, a physiologically occurring intracellular polymerase chain reaction, iPCR, a "Two-Tier Paradox" and RNA "Dark Matter". RNA-dependent mRNA amplification represents a new mode of genomic protein-encoding information transfer in mammalian cells. Its potential physiological impact is substantial, it appears relevant to multiple pathologies and its understanding opens new venues of therapeutic interference, it suggests powerful novel bioengineering approaches and its further rigorous investigations are highly warranted.

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News from Mars: Two-Tier Paradox, Intracellular PCR, Chimeric Junction Shift, Dark Matter mRNA and Other Remarkable Features of Mammalian RNA-Dependent mRNA Amplification. Implications for Alzheimer's Disease, RNA-Based Vaccines and mRNA Therapeutics. AD "Statin": Alzheimer's Disorder is a "Fast" Disease Preventable by Therapeutic Intervention Initiated Even Late in Life and Reversible at the Early Stages. Alzheimer's Disease is Driven by Intraneuronally Retained Beta-Amyloid Produced in the AD-Specific, βAPP-Independent Pathway: Current Perspective and Experimental Models for Tomorrow. Alzheimer's Disease Prevention and Treatment: Case for Optimism. Alzheimer’s Disease is Driven by Beta-Amyloid Generated in the Amyloid Precursor Protein-Independent Pathway and Retained Intraneuronally: Research and Therapeutic Strategies in a New AD Paradigm
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