氨基酰-tRNA合成酶编校功能缺陷引发的疾病  

The diseases induced by the editing deficient aminoacyl-tRNA synthetase

作　　者：纪泉泉 王恩多[1,3] 

机构地区：[1]中国科学院上海生物化学与细胞生物学研究所分子细胞科学卓越创新中心国家分子生物学重点实验室,上海200031 [2]中国科学院大学,北京100864 [3]上海科技大学生命科学与技术学院,上海201210

出　　处：《生命科学》2017年第6期521-526,共6页Chinese Bulletin of Life Sciences

基　　金：国家自然科学基金项目(91440204)

摘　　要：氨基酰-tRNA合成酶(aminoacyl-tRNA synthetase,aa RS)负责催化氨基酸与对应的tRNA生成氨基酰-tRNA,参与蛋白质的生物合成。aaRS除可以活化其对应的氨基酸外,也可误活化一些与对应氨基酸相似的非对应氨基酸。基于此,aaRS进化出一种编校功能,可以水解误活化或误氨基酰化的氨基酸,保证翻译的正确进行。一旦某种特定的aaRS的编校功能受损,会导致非对应氨基酸误掺入蛋白质,引起蛋白质误折叠。细胞通过上调热休克蛋白来帮助误折叠蛋白质重折叠。误折叠的蛋白质可能会聚集,引起ER应激,或通过泛素化-蛋白酶体途径降解。若超过细胞修复功能所能承受的范围,细胞会凋亡,对于多细胞生物来说,可能会引起一系列疾病,而对于单细胞生物来说,生长会受到抑制,严重的会直接死亡。Aminoacyl-tRNA synthetase（aaRS） are responsible for charging amino acids to the cognate tRNA to form aminoacyl-tRNAs, which are used for protein synthesis. Besides the cognate amino acids, aaRS could also misactivate other amino acids which share similar structures with the cognate amino acids. Therefore, aaRS evolve the editing function to hydrolyze the misactivated or misaminoacylated amino acids to ensure the translation fidelity. Once the editing function is disrupted, non-cognate amino acids would be misincorporated into the proteins, inducing protein misfolding. The misfolded proteins may be aggregated and induce the ER stress, further they could be degraded through the ubiquitin-proteosome pathway or autophagy. If the misfolded proteins are overloaded, the apoptosis would occur. For the multicellular organisms, the mistranslation may induce series of diseases, and for the unicellular organisms, the mistranslation may lead to cell growth delay or death.

关 键 词：氨基酰-TRNA合成酶 编校缺陷 生长抑制 疾病 

分 类 号：Q559[生物学—生物化学] Q78