Biomedical Center, Department of Physiological Chemistry, Ludwig-Maximilians-Universität München, Großhaderner Str. 9, 82152 Martinsried-Planegg, Germany.
Biomedical Center, Department of Physiological Chemistry, Ludwig-Maximilians-Universität München, Großhaderner Str. 9, 82152 Martinsried-Planegg, Germany; Center for Integrated Protein Science Munich (CIPSM) at the Department of Chemistry, Ludwig-Maximilians-Universität München, Munich, Germany.
Semin Cell Dev Biol. 2020 Aug;104:65-80. doi: 10.1016/j.semcdb.2020.02.003. Epub 2020 Feb 15.
Animals possess a wide variety of muscle types that support different kinds of movements. Different muscles have distinct locations, morphologies and contractile properties, raising the question of how muscle diversity is generated during development. Normal aging processes and muscle disorders differentially affect particular muscle types, thus understanding how muscles normally develop and are maintained provides insight into alterations in disease and senescence. As muscle structure and basic developmental mechanisms are highly conserved, many important insights into disease mechanisms in humans as well as into basic principles of muscle development have come from model organisms such as Drosophila, zebrafish and mouse. While transcriptional regulation has been characterized to play an important role in myogenesis, there is a growing recognition of the contributions of alternative splicing to myogenesis and the refinement of muscle function. Here we review our current understanding of muscle type specific alternative splicing, using examples of isoforms with distinct functions from both vertebrates and Drosophila. Future exploration of the vast potential of alternative splicing to fine-tune muscle development and function will likely uncover novel mechanisms of isoform-specific regulation and a more holistic understanding of muscle development, disease and aging.
动物拥有各种各样的肌肉类型，这些肌肉类型支持不同类型的运动。不同的肌肉具有不同的位置、形态和收缩特性，这就提出了一个问题，即在发育过程中，肌肉多样性是如何产生的。正常的衰老过程和肌肉疾病会对特定的肌肉类型产生不同的影响，因此了解肌肉的正常发育和维持方式可以深入了解疾病和衰老过程中的变化。由于肌肉结构和基本发育机制高度保守，许多关于人类疾病机制的重要见解以及关于肌肉发育的基本原理都来自于模式生物，如果蝇、斑马鱼和老鼠。虽然转录调控已被证明在肌发生中起着重要作用，但人们越来越认识到可变剪接对肌发生和肌肉功能的精细化的贡献。在这里，我们使用来自脊椎动物和果蝇的具有不同功能的异构体的例子，回顾我们对肌肉类型特异性可变剪接的现有认识。未来对可变剪接在微调肌肉发育和功能方面的巨大潜力的探索，很可能会揭示出同工型特异性调节的新机制，并对肌肉发育、疾病和衰老有更全面的认识。
