Abstract
Protein methyltransferases play various physiological and pathological roles through methylating histone and non-histone targets. Many histone methyltransferases have been reported to regulate the development of spermatogenic cells. However, the specific function of non-histone methyltransferases during spermatogenesis remains unclear. In this study, we found that METTL21A, a non-histone methyltransferase, is highly expressed in mouse testes. In order to elucidate the role of METTL21A in spermatogenesis, we generated a Mettl21a global knockout mouse model using CRISPR/Cas9 technology. Unexpectedly, our results showed that knockout males are fertile without apparent defects in the processes of male germ cell development, including spermatogonial differentiation, meiosis, and sperm maturation. Furthermore, the ablation of METTL21A does not affect the expression and localization of its known targeting proteins in testes. Together, our data demonstrated that METTL21A is not essential for mouse spermatogenesis and male fertility.
Highlights
Spermatogenesis is an extremely complex developmental process and involves the orderly differentiation of multiple types of spermatogenic cells, including mitotically proliferating spermatogonial cells, meiotically dividing spermatocytes, and spermatids that eventually mature into spermatozoa [1]
H3 lysine 9 tri-methylation (H3K9me3) [5]; combined depletion of EZH1 and EZH2, which are two protein methyltransferase that cause a depletion of global H3K27me3 marks and meiotic arrest in spermatocytes [6]; and conditional ablation of SETD2, a key methyltransferase catalyzing the trimethylation of histone H3 lysine 36 (H3K36me3), results in aberrant spermiogenesis with acrosomal malformation, leading to complete infertility [7]
The results showed that both mRNA and protein levels of Mettl21a are predominantly expressed in testis, followed by ovary, brain, and stomach (Figure 1b–d)
Summary
Spermatogenesis is an extremely complex developmental process and involves the orderly differentiation of multiple types of spermatogenic cells, including mitotically proliferating spermatogonial cells, meiotically dividing spermatocytes, and spermatids that eventually mature into spermatozoa [1]. METTL21E was previously demonstrated to maintain myofiber size by inhibiting proteasome-mediated protein degradation [12] Among these METTL21 methyltransferases, METTL21A is the member with the most known target proteins reported so far [13]. To investigate the role of METTL21A in male germ cell development and spermatogenesis, we first detected the expression of METTL21A in various mouse tissues. We found that it was predominantly expressed in testes, prompting us to establish. Our data revealed that Mettl21a knockout mice were completely fertile without any defects in the processes of germ cell development, including spermatogonial differentiation, meiosis, and sperm maturation. We found that Mettl21a ablation does not influence the expression level and subcellular localization of its target proteins
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