Defective mitochondrial mRNA maturation is associated with spastic ataxia

In human mitochondria, polyadenylation of mRNA, undertaken by the nuclear-encoded mitochondrial poly(A) RNA polymerase, is essential for maintaining mitochondrial gene expression. Our molecular investigation of an autosomal-recessive spastic ataxia with optic atrophy, present among the Old Order Amish, identified a mutation of MTPAP associated with the disease phenotype. When subjected to poly(A) tail-length assays, mitochondrial mRNAs from affected individuals were shown to have severely truncated poly(A) tails. Although defective mitochondrial DNA maintenance underlies a well-described group of clinical disorders, our findings reveal a defect of mitochondrial mRNA maturation associated with human disease and imply that this disease mechanism should be considered in other complex neurodegenerative disorders.     

陆地棉线粒体nad6基因mRNA无常规终止密码子

植物线粒体nad6基因编码NADH（还原型辅酶Ⅰ）脱氢酶第6亚基,前期研究发现,该基因可能与棉花细胞质雄性不育相关,但该基因的转录情况尚不清楚.本研究利用PCR测序、Southern印迹方法发现,陆地棉线粒体基因组（mtDNA）中nad6基因长621 bp,且为单拷贝. RT-PCR及环化RT-PCR分析发现,其mRNA在终止密码子前-14或-15 nt处提前终止|虽然该基因mRNA编码区存在12处RNA编辑（C-U）位点,但并未产生新的替代的终止密码子|基因mRNAs尾端poly（A）处含有0、1、2或4个“A”,也并未与前方相邻碱基凑成新的终止密码子,即：该基因mRNA无常规终止密码子（UGA,UAG,UAA）.本研究结果提示,棉花线粒体nad6基因mRNA很可能有其它的终止密码子.针对这种情况对植物线粒体如何翻译无常规终止密码子的mRNA进行了讨论.