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中心分子生物学教条进化中的RNA革命

The RNA Revolution in the Central Molecular Biology Dogma Evolution.

作者信息

Haseltine William A, Patarca Roberto

机构信息

Access Health International, 384 West Lane, Ridgefield, CT 06877, USA.

Feinstein Institutes for Medical Research, 350 Community Dr, Manhasset, NY 11030, USA.

出版信息

Int J Mol Sci. 2024 Nov 26;25(23):12695. doi: 10.3390/ijms252312695.

Abstract

Human genome projects in the 1990s identified about 20,000 protein-coding sequences. We are now in the RNA revolution, propelled by the realization that genes determine phenotype beyond the foundational central molecular biology dogma, stating that inherited linear pieces of DNA are transcribed to RNAs and translated into proteins. Crucially, over 95% of the genome, initially considered junk DNA between protein-coding genes, encodes essential, functionally diverse non-protein-coding RNAs, raising the gene count by at least one order of magnitude. Most inherited phenotype-determining changes in DNA are in regulatory areas that control RNA and regulatory sequences. RNAs can directly or indirectly determine phenotypes by regulating protein and RNA function, transferring information within and between organisms, and generating DNA. RNAs also exhibit high structural, functional, and biomolecular interaction plasticity and are modified via editing, methylation, glycosylation, and other mechanisms, which bestow them with diverse intra- and extracellular functions without altering the underlying DNA. RNA is, therefore, currently considered the primary determinant of cellular to populational functional diversity, disease-linked and biomolecular structural variations, and cell function regulation. As demonstrated by RNA-based coronavirus vaccines' success, RNA technology is transforming medicine, agriculture, and industry, as did the advent of recombinant DNA technology in the 1980s.

摘要

20世纪90年代的人类基因组计划识别出了约2万个蛋白质编码序列。我们现在正处于RNA革命之中,这是由一种认识推动的,即基因决定表型的方式超出了基础的中心分子生物学教条,该教条认为,遗传的线性DNA片段被转录为RNA,然后被翻译成蛋白质。至关重要的是,最初被认为是蛋白质编码基因之间的垃圾DNA的基因组中,超过95%编码着重要的、功能多样的非蛋白质编码RNA,这使得基因数量增加了至少一个数量级。DNA中大多数遗传性的决定表型的变化都发生在控制RNA和调控序列的区域。RNA可以通过调节蛋白质和RNA的功能、在生物体内部和之间传递信息以及生成DNA,直接或间接地决定表型。RNA还表现出高度的结构、功能和生物分子相互作用可塑性,并通过编辑、甲基化、糖基化和其他机制进行修饰,这些机制赋予它们多种细胞内和细胞外功能,而不会改变 underlying DNA。因此,目前RNA被认为是细胞到群体功能多样性、疾病相关和生物分子结构变异以及细胞功能调节的主要决定因素。正如基于RNA的冠状病毒疫苗的成功所证明的那样,RNA技术正在改变医学、农业和工业,就像20世纪80年代重组DNA技术的出现一样。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b9ee/11641533/466e5ad31a3e/ijms-25-12695-g001.jpg

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