Daneshpour Arian, Rezvanimehr Ali, Niktalab Pegah, Sharif Helia, Yazdanpanah Niloufar, Saleki Kiarash, Rezaei Nima
Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Tehran, 1416634793, Iran.
Faculty of Medicine, Tehran Medical Science Branch, Islamic Azad University, Tehran, 1651153311, Iran.
Rev Neurosci. 2024 Nov 25;36(3):327-338. doi: 10.1515/revneuro-2024-0112. Print 2025 Apr 28.
Vault RNAs (vtRNAs) are a novel group of non-coding RNAs that are involved in various signaling mechanisms. vtRNAs are joined by three proteins major vault protein (MVP), vault poly (ADP-ribose) polymerase (VPARP), and telomerase-associated protein 1 (TEP1) to form the vault complex. In humans, only four vtRNA including vtRNA 1-1, vtRNA 1-2, vtRNA 1-3, vtRNA 2-1) have been discovered. In nerve cells, vtRNA is involved in synapse formation through MAPK signaling. vtRNA travels to the distal area of neurites as a key unit in the vault complex. Moreover, tRNA is detached from the vault complex in the neurite via a mitotic kinase Aurora-A-reliant MVP phosphorylation. Several molecules contribute to the formation of vtRNAs. For instance, SRSF2 and NSUN2 and their attachment to vtRNA1-1 determines the production of small-vtRNAs. Through the same factors, vtRNAs could play a role in neurodevelopmental deficits. Addition the role of vtRNA expression and vault proteins has been recently studied in neurodegenerative disorders such as Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS) as well as brain cancers. While the mechanisms of vtRNA involvement in neurological disorders is not well-demonstrated, we believe this could be related to the impact of vtRNA regulation in autophagy, immunoregulation, RNA stability, cellular stress, apoptosis, and regulation of other epigenetic pathways. The present review captures the state-of-the-art regarding the role of vtRNAs in neurodevelopment, normal nervous system function, and neurological disorders.
穹窿体RNA（vtRNAs）是一类新型的非编码RNA，参与多种信号传导机制。vtRNAs与三种蛋白质——主要穹窿体蛋白（MVP）、穹窿体聚（ADP-核糖）聚合酶（VPARP）和端粒酶相关蛋白1（TEP1）结合，形成穹窿体复合物。在人类中，仅发现了四种vtRNA，即vtRNA 1-1、vtRNA 1-2、vtRNA 1-3、vtRNA 2-1。在神经细胞中，vtRNA通过丝裂原活化蛋白激酶（MAPK）信号传导参与突触形成。vtRNA作为穹窿体复合物中的关键单元，向神经突的远端区域移动。此外，tRNA通过依赖有丝分裂激酶极光激酶A（Aurora-A）的MVP磷酸化作用，在神经突中从穹窿体复合物上脱离。有几种分子参与了vtRNAs的形成。例如，丝氨酸/精氨酸丰富剪接因子2（SRSF2）和Nsun2甲基转移酶2（NSUN2）及其与vtRNA1-1的结合决定了小vtRNAs的产生。通过相同的因素，vtRNAs可能在神经发育缺陷中发挥作用。此外，最近还研究了vtRNA表达和穹窿体蛋白在神经退行性疾病如阿尔茨海默病（AD）、帕金森病（PD）、多发性硬化症（MS）、亨廷顿舞蹈病（HD）和肌萎缩侧索硬化症（ALS）以及脑癌中的作用。虽然vtRNA参与神经系统疾病的机制尚未得到充分证实，但我们认为这可能与vtRNA调节自噬、免疫调节、RNA稳定性、细胞应激、凋亡以及其他表观遗传途径的影响有关。本综述阐述了关于vtRNAs在神经发育、正常神经系统功能和神经系统疾病中作用的最新研究进展。
