摘要
RNA结合蛋白(mtRBP)介导的mRNA转录后调节对精子发生必不可少但却鲜有报道.在本文中,我们鉴定到一个在生殖腺中特异性表达的线粒体RNA结合蛋白AMG-1,它是秀丽隐杆线虫精子发生过程中必需的蛋白,同时与哺乳动物LRPPRC蛋白同源.amg-1突变会阻碍生殖腺的发育,最终导致生殖细胞的线粒体形态和结构异常以及线粒体功能障碍.通过测序鉴定RNA结合蛋白的靶点发现,AMG-1更倾向于与mtDNA编码的参与线粒体核糖体组装的12S和16S核糖体RNA(rRNA)结合,12S rRNA对于维持生殖细胞线粒体蛋白稳态至关重要,而12S rRNA的表达却受AMG-1蛋白调节.此外,哺乳动物SLIRP在秀丽线虫中的同源蛋白SLRP-1蛋白与AMG-1在遗传上存在互作关系,它们可共同调节秀丽线虫的精子发生和育性.综上所述,这些发现揭示了mtRBP蛋白AMG-1在线粒体调控中的新机制,这可能为由线粒体功能障碍引发的男性不育治疗提供新的理论基础.
The mechanisms of RNA-binding proteins(RBPs)-mediated post-transcriptional regulation of preexisting mRNAs,which is essential for spermatogenesis,remain poorly understood.In this study,we identify that a germline-specific mitochondrial RBP AMG-1(abnormal mitochondria in germline 1),a homolog of mammalian leucine-rich PPR motif-containing protein(LRPPRC),is required for spermatogenesis in Caenorhabditis elegans.The amg-1 mutation hinders germline development without affecting somatic development and leads to the aberrant mitochondrial morphology and structure associated with mitochondrial dysfunctions specifically in the germline.We demonstrate that AMG-1 is most frequently bound to mtDNA-encoded 12S and 16S ribosomal RNA,the essential components of mitochondrial ribosomes,and that 12S rRNA expression mediated by AMG-1 is crucial for germline mitochondrial protein homeostasis.Furthermore,steroid receptor RNA activator(SRA)stem loop interacting RNA binding protein(SLRP-1),a homolog of mammalian SRA stem loop interacting RNA binding protein(SLIRP)in C.elegans,interacts with AMG-1 genetically to regulate germline development and reproductive success in C.elegans.Overall,these findings reveal the novel function of mt RBP,specifically in regulating germline development.
作者
王鹏
王秋实
陈联万
曹铮
赵海莲
苏瑞宝
王宁
马肖静
单进
陈新艳
张琦
杜宝臣
袁志恒
赵艳梅
张晓荣
郭雪江
薛愿超
苗龙
Peng Wang;Qiushi Wang;Lianwan Chen;Zheng Cao;Hailian Zhao;Ruibao Su;Ning Wang;Xiaojing Ma;Jin Shan;Xinyan Chen;Qi Zhang;Baochen Du;Zhiheng Yuan;Yanmei Zhao;Xiaorong Zhang;Xuejiang Guo;Yuanchao Xue;Long Miao(Key Laboratory of RNA Biology,CAS Center for Excellence in Biomacromolecules,Institute of Biophysics,Chinese Academy of Sciences,Beijing 100101,China;University of Chinese Academy of Sciences,Beijing 100059,China;National Institute of Biological Sciences,Beijing 102206,China;Department of Automation,Tsinghua University,Beijing 100084,China;State Key Laboratory of Reproductive Medicine and Offspring Health,Department of Histology and Embryology,Nanjing Medical University,Nanjing 211166,China;Center for Biological Imaging,Core Facilities for Protein Science,Institute of Biophysics,Chinese Academy of Sciences,Beijing 100101,China;Key Laboratory of Cell Proliferation and Regulation Biology of Ministry of Education,College of Life Science,Beijing Normal University,Beijing 100875,China)
基金
supported by the National Natural Science Foundation of China(32270774,31671400,81971439,32070694,31571436,31872822,and 31301153)
the National Key Research and Development Program of China(2017YFA0503502,2016YFA0500903,2021YFC2700200,2017YFA0504600,and 2019YFA0508700)
funded by the National Institutes of Health Office of Research Infrastructure Programs(P40 OD010440)。
