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

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 (Delta RING-TRIM41) and found that Delta RING-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. Author summaryDuring the meiotic prophase, germ cells undergo various characteristic events such as a physical linkage of homologous chromosomes (termed synapsis). This linkage of homologous chromosomes is known to be established by a homology search. However, most mammals have heteromorphic sex chromosomes (X and Y) with a small region of homology, which entails exceptional and specialized responses such as physical sequestration into a membrane-less organelle (termed XY body). Characterization of essential molecules will be the key to clarifying the mechanism of these events and meiosis. In this study, we identified tripartite motif-containing 41 (TRIM41) a ubiquitin ligase E3, as an essential factor for proper synapsis configuration and XY body formation. The most striking phenotype of Trim41-deficient spermatocytes was a misregulation of axis protein dynamics such as synaptonemal complex protein 3 (SYCP3) and SYCP1, which was mainly observed on the X chromosome. These results suggested that TRIM41 might be essential for chromosome axis remodeling during meiotic progression.