Hsu Ho-Chiang, Hsu Sheng-Ping, Hsu Fang-Yu, Chang Mien, Chen Jun-An
Institute of Molecular Biology, Academia Sinica, Taipei 11529, Taiwan.
Taiwan International Graduate Program in Interdisciplinary Neuroscience, National Cheng Kung University and Academia Sinica, Taipei, Taiwan.
iScience. 2024 Feb 10;27(3):109207. doi: 10.1016/j.isci.2024.109207. eCollection 2024 Mar 15.
Long noncoding RNAs (lncRNAs) play pivotal roles in modulating gene expression during development and disease. Despite their high expression in the central nervous system (CNS), understanding the precise physiological functions of CNS-associated lncRNAs has been challenging, largely due to the -centric nature of studies in this field. Here, utilizing mouse embryonic stem cell (ESC)-derived motor neurons (MNs), we identified an unexplored MN-specific lncRNA, (ong nergenic RNAs in at ntron). By employing an "exon-only" deletion strategy in ESCs and a mouse model, we reveal that deletion profoundly impacts MN dendritic complexity, axonal growth, and altered action potential patterns. Mechanistically, voltage-gated channels and neurite growth-related genes exhibited heightened sensitivity to deletion. Our -knockout mouse model displayed compromised motor behaviors and reduced muscle strength, highlighting 's critical role in motor function. This study unveils an underappreciated function of lncRNAs in orchestrating MN maturation and maintaining robust electrophysiological properties.
长链非编码RNA（lncRNAs）在发育和疾病过程中调节基因表达方面发挥着关键作用。尽管它们在中枢神经系统（CNS）中高表达，但了解与CNS相关的lncRNAs的确切生理功能一直具有挑战性，这主要是由于该领域研究以基因为中心的性质。在这里，利用小鼠胚胎干细胞（ESC）衍生的运动神经元（MNs），我们鉴定出一种未被探索的MN特异性lncRNA，（内含子中的长神经源性RNA）。通过在ESC和小鼠模型中采用“仅外显子”缺失策略，我们发现缺失会深刻影响MN的树突复杂性、轴突生长并改变动作电位模式。从机制上讲，电压门控通道和神经突生长相关基因对缺失表现出更高的敏感性。我们的基因敲除小鼠模型表现出运动行为受损和肌肉力量下降，突出了在运动功能中的关键作用。这项研究揭示了lncRNAs在协调MN成熟和维持强大电生理特性方面未被充分认识的功能。
