Trim41 is required to regulate chromosome axis protein dynamics and meiosis in male mice

Seiya Oura; Toshiaki Hino; Takashi Satoh; Taichi Noda; Takayuki Koyano; Ayako Isotani; Makoto Matsuyama; Shizuo Akira; Kei-Ichiro Ishiguro; Masahito Ikawa

doi:10.1371/journal.pgen.1010241

Trim41 is required to regulate chromosome axis protein dynamics and meiosis in male mice

PLoS Genet. 2022 Jun 1;18(6):e1010241. doi: 10.1371/journal.pgen.1010241. eCollection 2022 Jun.

Authors

Seiya Oura^{1

2}, Toshiaki Hino³, Takashi Satoh^{4

5

6}, Taichi Noda^{1

7

8}, Takayuki Koyano⁹, Ayako Isotani^{1

10}, Makoto Matsuyama⁹, Shizuo Akira^{5

6}, Kei-Ichiro Ishiguro¹¹, Masahito Ikawa^{1

2

12

13}

Affiliations

¹ Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
² Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, Japan.
³ Department of Biological Sciences, Asahikawa Medical University, Asahikawa, Japan.
⁴ Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
⁵ Laboratory of Host Defense, WPI Immunology Frontier Research Center, Osaka University, Osaka, Japan.
⁶ Department of Immune Regulation, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
⁷ Priority Organization for Innovation and Excellence, Kumamoto University, Kumamoto, Japan.
⁸ Division of Reproductive Biology, Institute of Resource Development and Analysis, Kumamoto University, Kumamoto, Japan.
⁹ Division of Molecular Genetics, Shigei Medical Research Institute, Okayama, Japan.
¹⁰ Division of Biological Science, Graduate School of Science and Technology, Nara Institute of Science and Technology, Nara, Japan.
¹¹ Department of Chromosome Biology, Institute of Molecular Embryology and Genetics (IMEG), Kumamoto University, Kumamoto, Japan.
¹² The Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo, Japan.
¹³ Center for Infectious Disease Education and Research (CiDER), Osaka University, Osaka, Japan.

Abstract

Meiosis is a hallmark event in germ cell development that accompanies sequential events executed by numerous molecules. Therefore, characterization of these factors is one of the best strategies to clarify the mechanism of meiosis. Here, we report tripartite motif-containing 41 (TRIM41), a ubiquitin ligase E3, as an essential factor for proper meiotic progression and fertility in male mice. Trim41 knockout (KO) spermatocytes exhibited synaptonemal complex protein 3 (SYCP3) overloading, especially on the X chromosome. Furthermore, mutant mice lacking the RING domain of TRIM41, required for the ubiquitin ligase E3 activity, phenocopied Trim41 KO mice. We then examined the behavior of mutant TRIM41 (ΔRING-TRIM41) and found that ΔRING-TRIM41 accumulated on the chromosome axes with overloaded SYCP3. This result suggested that TRIM41 exerts its function on the chromosome axes. Our study revealed that Trim41 is essential for preventing SYCP3 overloading, suggesting a TRIM41-mediated mechanism for regulating chromosome axis protein dynamics during male meiotic progression.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cell Cycle Proteins / genetics
Cell Cycle Proteins / metabolism
Male
Meiosis / genetics
Mice
Mice, Knockout
Nuclear Proteins* / genetics
Nuclear Proteins* / metabolism
Spermatocytes / metabolism
Synaptonemal Complex* / genetics
Synaptonemal Complex* / metabolism
Ubiquitin-Protein Ligases / genetics
Ubiquitin-Protein Ligases / metabolism*

Substances

Cell Cycle Proteins
Nuclear Proteins
Trim41 protein, mouse
Ubiquitin-Protein Ligases

Grants and funding

This work was supported by: the Japan Society for the Promotion of Science (JSPS) KAKENHI grants (JP19J21619 to S.O., JP19H05758 to T.H., JP18K14612 and JP20H03172 to T.N., 19H05743 to KI, and JP19H05750 and 21H04753 to M.I.); Takeda Science Foundation Grants to T.N. and M.I.; The Nakajima Foundation to T.N.; and the Bill & Melinda Gates Foundation (INV-001902 to M.I.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.