Elucidation of causative mechanism of amyotrophic lateral sclerosis via abnormality of methylation of TLS and development of its therapeutics.

rna结合蛋白TLS已被报道为肌萎缩性侧索硬化症（ALS）的致病基因。在als突变体中，TLS失去了蛋白精氨酸n -甲基转移酶5 （PRMT 5）的结合。然后，我们假设突变的TLS可能是由于精氨酸特异性甲基化缺失引起的蛋白质结合异常导致的不溶性聚集体的形成而导致ALS的。本研究的具体目的是证明这一假设，并生成一种“RNA配体”来恢复PRMT5与TLS的结合。然后，我们发现了TLS精氨酸甲基化的新机制，并在RNA配体的生成方面取得了重大进展

RNA-binding protein TLS has been reported as a causative gene for amyotrophic lateral sclerosis (ALS). At the ALS-mutant TLS lost binding of protein arginine N-methyltransferase 5 (PRMT 5). Then, we hypothesize that the mutated TLS should cause ALS through formation of the insoluble aggregates induced by abnormality of binding of proteins elicited with deletion of arginine-specific methylation. Specific aim of the study is to prove the hypothesis and generate an “RNA ligand” to recover the binding of PRMT5 to TLS. Then, we have shown novel mechanism of arginine-methylation of TLS and attained significant progress in generating the RNA ligand