Nazim Mohammad
Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, United States.
Front Mol Neurosci. 2024 Dec 23;17:1483901. doi: 10.3389/fnmol.2024.1483901. eCollection 2024.
Post-transcriptional mechanisms, such as alternative splicing and polyadenylation, are recognized as critical regulatory processes that increase transcriptomic and proteomic diversity. The advent of next-generation sequencing and whole-genome analyses has revealed that numerous transcription and epigenetic regulators, including transcription factors and histone-modifying enzymes, undergo alternative splicing, most notably in the nervous system. Given the complexity of regulatory processes in the brain, it is conceivable that many of these splice variants control different aspects of neuronal development. Mutations or dysregulation of splicing and transcription regulatory proteins are frequently linked to various neurodevelopmental disorders, highlighting the importance of understanding the role of neuron-specific alternative splicing in maintaining proper transcriptional regulation in the brain. This review consolidates current insights into the role of alternative splicing in influencing transcriptional and chromatin regulatory programs in neuronal development.
转录后机制，如可变剪接和多聚腺苷酸化，被认为是增加转录组和蛋白质组多样性的关键调控过程。新一代测序和全基因组分析的出现揭示了许多转录和表观遗传调节因子，包括转录因子和组蛋白修饰酶，都经历可变剪接，最显著的是在神经系统中。鉴于大脑中调控过程的复杂性，可以想象这些剪接变体中的许多控制着神经元发育的不同方面。剪接和转录调节蛋白的突变或失调经常与各种神经发育障碍相关联，这突出了理解神经元特异性可变剪接在维持大脑中适当转录调控方面作用的重要性。本综述整合了当前对可变剪接在影响神经元发育中转录和染色质调控程序方面作用的见解。
