A-to-I RNA 编辑、M6A RNA 甲基化和可变剪接对生理脑衰老和神经退行性疾病的贡献。
Contribution of A-to-I RNA editing, M6A RNA Methylation, and Alternative Splicing to physiological brain aging and neurodegenerative diseases.
机构信息
Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy; Department of Experimental Medicine, University of Rome Tor Vergata, Rome, Italy.
Division of Neuroscience, Department of Psychology, Sapienza University of Rome, Rome, Italy; European Center for Brain Research, IRCCS Fondazione Santa Lucia, Rome, Italy.
出版信息
Mech Ageing Dev. 2023 Jun;212:111807. doi: 10.1016/j.mad.2023.111807. Epub 2023 Apr 5.
Aging is a physiological and progressive phenomenon in all organisms' life cycle, characterized by the accumulation of degenerative processes triggered by several alterations within molecular pathways. These changes compromise cell fate, resulting in the loss of functions in tissues throughout the body, including the brain. Physiological brain aging has been linked to structural and functional alterations, as well as to an increased risk of neurodegenerative diseases. Post-transcriptional RNA modifications modulate mRNA coding properties, stability, translatability, expanding the coding capacity of the genome, and are involved in all cellular processes. Among mRNA post-transcriptional modifications, the A-to-I RNA editing, m6A RNA Methylation and Alternative Splicing play a critical role in all the phases of a neuronal cell life cycle and alterations in their mechanisms of action significantly contribute to aging and neurodegeneration. Here we review our current understanding of the contribution of A-to-I RNA editing, m6A RNA Methylation, and Alternative Splicing to physiological brain aging process and neurodegenerative diseases.
衰老是所有生物生命周期中的一种生理和渐进现象，其特征是分子途径内的几种改变引发的退行性过程的积累。这些变化危及细胞命运，导致全身组织（包括大脑）功能丧失。生理脑衰老与结构和功能改变有关，也与神经退行性疾病的风险增加有关。转录后 RNA 修饰调节 mRNA 的编码特性、稳定性和翻译能力，扩展基因组的编码能力，并参与所有细胞过程。在 mRNA 转录后修饰中，A 到 I 的 RNA 编辑、m6A RNA 甲基化和可变剪接在神经元细胞生命周期的所有阶段都起着关键作用，其作用机制的改变对衰老和神经退行性变有重要贡献。在这里，我们回顾了我们对 A 到 I 的 RNA 编辑、m6A RNA 甲基化和可变剪接对生理脑衰老过程和神经退行性疾病的贡献的理解。
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