秀丽隐杆线虫RNA结合蛋白复合物AMG-1/SLRP-1通过线粒体稳态维持实现调控生殖腺发育和精子发生  

RNA-binding protein complex AMG-1/SLRP-1 mediates germline development and spermatogenesis by maintaining mitochondrial homeostasis in Caenorhabditis elegans

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)

机构地区：[1]Key Laboratory of RNA Biology,CAS Center for Excellence in Biomacromolecules,Institute of Biophysics,Chinese Academy of Sciences,Beijing 100101,China [2]University of Chinese Academy of Sciences,Beijing 100059,China [3]National Institute of Biological Sciences,Beijing 102206,China [4]Department of Automation,Tsinghua University,Beijing 100084,China [5]State Key Laboratory of Reproductive Medicine and Offspring Health,Department of Histology and Embryology,Nanjing Medical University,Nanjing 211166,China [6]Center for Biological Imaging,Core Facilities for Protein Science,Institute of Biophysics,Chinese Academy of Sciences,Beijing 100101,China [7]Key Laboratory of Cell Proliferation and Regulation Biology of Ministry of Education,College of Life Science,Beijing Normal University,Beijing 100875,China

出　　处：《Science Bulletin》2023年第13期1399-1412,M0004,共15页科学通报（英文版）

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)。

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.

关 键 词：SPERMATOGENESIS RNA-binding protein mt-rRNA MITOCHONDRIA Caenorhabditis elegans 

分 类 号：Q132[生物学—普通生物学]