Marasco Luciano E, Kornblihtt Alberto R
Universidad de Buenos Aires (UBA), Facultad de Ciencias Exactas y Naturales, Departamento de Fisiología, Biología Moleculary Celular and CONICET-UBA, Instituto de Fisiología, Biología Molecular y Neurociencias (IFIBYNE), Buenos Aires, Argentina.
Sir William Dunn School of Pathology, University of Oxford, Oxford, UK.
Nat Rev Mol Cell Biol. 2023 Apr;24(4):242-254. doi: 10.1038/s41580-022-00545-z. Epub 2022 Oct 13.
Alternative splicing is a substantial contributor to the high complexity of transcriptomes of multicellular eukaryotes. In this Review, we discuss the accumulated evidence that most of this complexity is reflected at the protein level and fundamentally shapes the physiology and pathology of organisms. This notion is supported not only by genome-wide analyses but, mainly, by detailed studies showing that global and gene-specific modulations of alternative splicing regulate highly diverse processes such as tissue-specific and species-specific cell differentiation, thermal regulation, neuron self-avoidance, infrared sensing, the Warburg effect, maintenance of telomere length, cancer and autism spectrum disorders (ASD). We also discuss how mastering the control of alternative splicing paved the way to clinically approved therapies for hereditary diseases.
可变剪接是多细胞真核生物转录组高度复杂性的一个重要促成因素。在本综述中，我们讨论了越来越多的证据，表明这种复杂性大多在蛋白质水平上得以体现，并从根本上塑造了生物体的生理和病理状态。这一观点不仅得到了全基因组分析的支持，而且主要是通过详细研究得到证实，这些研究表明可变剪接的全局和基因特异性调控参与了多种不同的过程，如组织特异性和物种特异性细胞分化、体温调节、神经元自我回避、红外感应、瓦伯格效应、端粒长度维持、癌症和自闭症谱系障碍（ASD）。我们还讨论了掌握可变剪接的控制如何为遗传性疾病的临床批准疗法铺平了道路。
