Salvi Jayesh S, Mekhail Karim
a Department of Laboratory Medicine and Pathobiology; Faculty of Medicine ; University of Toronto ; Toronto , ON Canada.
Nucleus. 2015;6(1):23-9. doi: 10.1080/19491034.2015.1004952.
Amyotrophic lateral sclerosis (ALS) is a severely debilitating neurodegenerative disease linked to mutations in various genes implicated in cytoplasmic RNA metabolism. Recent studies from genetic models have also helped reveal connections between various ALS-linked factors and RNA-DNA hybrid (R-loop) regulation. Here, we examine how such hybrid-regulatory processes are pointing to a key role for the nucleus in ALS. We also present a potential molecular mechanism in which hybrids may represent at least one of the long sought after missing links between different ALS genes. Our opinion is that RNA-DNA hybrids will play a key role in deciphering ALS and other human diseases.
肌萎缩侧索硬化症（ALS）是一种严重使人衰弱的神经退行性疾病，与参与细胞质RNA代谢的各种基因突变有关。来自遗传模型的最新研究也有助于揭示各种与ALS相关的因素与RNA-DNA杂交体（R环）调控之间的联系。在这里，我们研究了这种杂交调控过程如何表明细胞核在ALS中起关键作用。我们还提出了一种潜在的分子机制，其中杂交体可能代表不同ALS基因之间长期寻找的缺失环节中的至少一个。我们认为RNA-DNA杂交体将在解读ALS和其他人类疾病中发挥关键作用。
