精神发育迟滞又叫智力发育障碍是指以智力发育不全或受阻和社会适应困难为主要特征的一组综合症，该疾病在人类中发病率在2-3%之间，其致病原因多种多样，其中X-连锁基因的缺陷是造成智力障碍综合症的重要原因之一。人FTSJ1就是其中一个X-连锁智力发育障碍基因，然而其功能和致病机制尚不清楚。根据蛋白质序列分析，人FTSJ1是一个核糖核酸（RNA）的核苷酸甲基化修饰酶，经过申请人前期研究工作鉴定，FTSJ1催化两种人胞质转运RNA(tRNA)反密码子环部分的核苷酸甲基化修饰。无独有偶，除FTSJ1外，还有多个RNA甲基化修饰酶功能缺陷被发现与神经认知疾病尤其是精神发育迟滞相关，然而RNA甲基化修饰与这类疾病之间的致病机理尚无相关报导。本申请拟以人FTSJ1基因作为研究对象，通过对其催化机理、三级结构和细胞内尤其是神经元内生理功能进行研究，试图初步了解tRNA甲基化酶FTSJ1与精神发育之间的关系。

Mental retardation also called Intellectual disability is a syndrome characterized by significantly impaired intellectual development or retardation and deficits in adaptive behaviors to social life. Intellectual disability syndrome widely happened in human being, the prevalence is thought to be on the order of 2-3%. Many genetic and environmental reasons can lead to mental retardation, of which the X-linked gene dysfunction is one of the most important causes. Human FTSJ1 is one of the X-linked intellectual disability genes; however the cellular function of FTSJ1 and its mechanism leading to mental retardation remains unclear. FTSJ1 is a putative RNA methyltransferase based on primary sequence alignment, and according to the unpublished data of the applier of this current proposal, FTSJ1 could catalyze the methylation of the anticodon region of two human cytosolic transfer RNAs (tRNAs). Besides FTSJ1, several other RNA methyltransferases were reported to be involved in neural cognitive diseases especially mental retardation, but the mechanism of RNA methylation and those diseases remain elusive. The current proposal will focus on FTSJ1 gene, through the study of its catalytic mechanism, crystal structure and cellular function especially in neurons; hopefully we will be able to figure out the relationship between FTSJ1 and intellectual development.