Positioning of sperm tail longitudinal columns depend on Nsun7, an RNA binding protein destabilizing elongated spermatid transcripts

  1. Petr V Sergiev16,17
  1. 1 Center of Molecular and Cellular Biology, Skolkovo Institute of Science and Technology; Belozersky Institute of Physico-Chemical Biology and Faculty of Chemistry, Lomonosov Moscow State University;;
  2. 2 Belozersky Institute of Physico-Chemical Biology and Faculty of Chemistry, Lomonosov Moscow State University;
  3. 3 Center for Brain Research, Medical University Vienna;
  4. 4 Faculty of Chemistry, Lomonosov Moscow State University;
  5. 5 Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University; Research Centre for Medical Genetics;
  6. 6 Faculty of Chemistry and Faculty of Bioengeneering and Bioinformatics, Lomonosov Moscow State University;
  7. 7 Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University;
  8. 8 Center of Molecular and Cellular Biology, Skolkovo Institute of Science and Technology; Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University;
  9. 9 National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I.Kulakov;
  10. 10 Institute of Biomedical Chemistry, 119121 Moscow, Russia;
  11. 11 Institute of gene biology;
  12. 12 Belgorod State University;
  13. 13 Institute of Biomedical Chemistry;
  14. 14 Institute of Bioengineering, Research Center of Biotechnology of the Russian Academy of Sciences;
  15. 15 Skolkovo Inst of Science & Technology; Lomonosov Moscow State Univ; Shemyakin-Ovchinnikov Institute;
  16. 16 Center of Molecular and Cellular Biology, Skolkovo Institute of Science and Technology; Belozersky Institute of Physico-Chemical Biology and Faculty of Chemistry, Lomonosov Moscow State University
  1. * Corresponding author; email: petya{at}genebee.msu.ru

Abstract

Spermatozoid’s flagella assemble in transcriptionally silent spermatids and thus depends on post-transcriptional regulation of gene expression. Mutations in Nsun7 gene are known to cause male infertility in human and mice. We identified m5C-specific Nsun7 RNA methyltransferase as a protein present in elongated spermatids and interacting with RNAs specific for this type of spermatozoid’s precursor cells. Inactivation of Nsun7 gene in mice leads to upregulation of its RNA interactors, thus indicating that Nsun7 downregulates a set of RNAs in the elongated spermatids. A physiologic consequence of Nsun7 gene knockout is male infertility, which is mechanistically explained by the observed mispositioning of longitudinal columns relative to the axonemal microtubular doublets leading to motility defect.

Keywords

  • Received November 10, 2024.
  • Accepted February 16, 2025.

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