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.
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.
Sci Bull (Beijing). 2023 Jul 15;68(13):1399-1412. doi: 10.1016/j.scib.2023.05.029. Epub 2023 May 24.
The mechanisms of RNA-binding proteins (RBPs)-mediated post-transcriptional regulation of pre-existing 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 mtRBP, specifically in regulating germline development.
RNA 结合蛋白(RBPs)介导的对预先存在的 mRNA 的转录后调控的机制,对于精子发生是至关重要的,但目前仍知之甚少。在这项研究中,我们鉴定出一个生殖细胞特异性的线粒体 RBP AMG-1(生殖细胞中线粒体异常 1),是哺乳动物亮氨酸丰富的 PPR 基序蛋白(LRPPRC)的同源物,在秀丽隐杆线虫中是精子发生所必需的。amg-1 突变阻碍了生殖细胞的发育,而不影响体细胞的发育,并导致与线粒体功能障碍相关的异常线粒体形态和结构,这种功能障碍仅发生在生殖细胞中。我们证明 AMG-1 最常与 mtDNA 编码的 12S 和 16S 核糖体 RNA 结合,这是线粒体核糖体的必需成分,并且由 AMG-1 介导的 12S rRNA 表达对于生殖细胞中线粒体蛋白的平衡至关重要。此外,类固醇受体 RNA 激活物(SRA)茎环相互作用 RNA 结合蛋白(SLRP-1),在秀丽隐杆线虫中是哺乳动物 SRA 茎环相互作用 RNA 结合蛋白(SLIRP)的同源物,与 AMG-1 在遗传上相互作用,以调节秀丽隐杆线虫的生殖细胞发育和生殖成功。总的来说,这些发现揭示了 mtRBP 的新功能,特别是在调节生殖细胞发育方面。