Abstract：
The U1 small ribonucleoprotein (U1 snRNP) plays a pivotal role in the intricate process of gene expression, specifically within nuclear RNA processing. By initiating the splicing reaction and modulating 3\'-end processing, U1 snRNP exerts precise control over RNA metabolism and gene expression. This ribonucleoparticle is abundantly present, and its complex biogenesis necessitates shuttling between the nuclear and cytoplasmic compartments. Over the past three decades, extensive research has illuminated the crucial connection between disrupted U snRNP biogenesis and several prominent human diseases, notably various neurodegenerative conditions. The perturbation of U1 snRNP homeostasis has been firmly established in diseases such as Spinal Muscular Atrophy, Pontocerebellar hypoplasia, and FUS-mediated Amyotrophic Lateral Sclerosis. Intriguingly, compelling evidence suggests a potential correlation in Fronto-temporal dementia and Alzheimer\'s disease as well. Although the U snRNP biogenesis pathway is conserved across all eukaryotic cells, neurons, in particular, appear to be highly susceptible to alterations in spliceosome homeostasis. In contrast, other cell types exhibit a greater resilience to such disturbances. This vulnerability underscores the intricate relationship between U1 snRNP dynamics and the health of neuronal cells, shedding light on potential avenues for understanding and addressing neurodegenerative disorders.
摘要：
U1小核糖核蛋白（U1snRNP）在复杂的基因表达过程中起着关键作用，特别是在核RNA加工中。通过启动剪接反应并调节3'端处理，U1snRNP精确控制RNA代谢和基因表达。这个核糖核酸颗粒大量存在，其复杂的生物发生需要在细胞核和细胞质区室之间穿梭。在过去的三十年里，广泛的研究阐明了破坏的UsnRNP生物发生与几种突出的人类疾病之间的关键联系，尤其是各种神经退行性疾病。U1snRNP稳态的扰动已经在脊髓性肌萎缩等疾病中得到了牢固的确立，前脑小脑发育不全,和FUS介导的肌萎缩侧索硬化。有趣的是，令人信服的证据表明，颞叶痴呆和阿尔茨海默病也存在潜在的相关性。尽管UsnRNP生物发生途径在所有真核细胞中是保守的，神经元，特别是,似乎极易受到剪接体稳态改变的影响。相比之下,其他细胞类型对这种干扰表现出更大的弹性。这种脆弱性强调了U1snRNP动力学与神经元细胞健康之间的复杂关系，揭示理解和解决神经退行性疾病的潜在途径。
