《生命科学》 2017, 29(6): 521-526

氨基酰-tRNA合成酶编校功能缺陷引发的疾病

纪泉泉1，2，王恩多1，3*

（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）

摘　要：摘　要：氨基酰-tRNA 合成酶(aminoacyl-tRNA synthetase， aaRS) 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。

The diseases induced by the editing deficient aminoacyl-tRNA synthetase

JI Quan-Quan1，2， WANG En-Duo1，3*

(1 State Key Laboratory of Molecular Biology， CAS Center for Excellence in Molecular Cell Science， Shanghai Institute of Biochemistry and Cell Biology， Chinese Academy of Sciences， Shanghai 200031， China; 2 University of Chinese Academy of Sciences， Beijing 100864， China; 3 School of Life Science and Technology， Shanghai Tech University， Shanghai 201210， China)

Abstract: Abstract: 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.