METTL21A, a non-histone methyltransferase, belongs to the methyltransferase-like (METTL) family. It has been shown to methylate single lysine residues in Hsp70 proteins, with the reaction stimulated by ATP. This methylation can alter the affinity of chaperones like HSPA8 (Hsc70) for certain proteins, suggesting its role in modulating protein-protein interactions and potentially in protein function regulation [3,4].

A global Mettl21a knockout mouse model generated using CRISPR/Cas9 technology demonstrated that METTL21A is dispensable for spermatogenesis and male fertility in mice. The knockout males were fertile with no apparent defects in male germ cell development processes such as spermatogonial differentiation, meiosis, and sperm maturation. Also, the ablation of METTL21A did not affect the expression and localization of its known targeting proteins in testes [1]. Additionally, exome-wide association study using whole-exome sequencing data from the UK Biobank identified METTL21A as a gene associated with varicose veins (VV), specifically in females [2].

In conclusion, METTL21A, as a non-histone methyltransferase, plays a role in protein methylation, especially of Hsp70 proteins. The gene knockout mouse model has revealed that it is not essential for spermatogenesis and male fertility. Its association with varicose veins in females from exome-sequencing studies also indicates its potential role in vascular-related diseases, expanding our understanding of its biological functions and disease associations.

References:

1. Li, Jinmei, Feng, Shenglei, Ma, Xixiang, Yuan, Shuiqiao, Wang, Xiaoli. 2022. METTL21A, a Non-Histone Methyltransferase, Is Dispensable for Spermatogenesis and Male Fertility in Mice. In International journal of molecular sciences, 23, . doi:10.3390/ijms23041942. https://pubmed.ncbi.nlm.nih.gov/35216057/

2. Zhang, Dan-Dan, He, Xiao-Yu, Yang, Liu, Tan, Lan, Yu, Jin-Tai. 2024. Exome sequencing identifies novel genetic variants associated with varicose veins. In PLoS genetics, 20, e1011339. doi:10.1371/journal.pgen.1011339. https://pubmed.ncbi.nlm.nih.gov/38980841/

3. Shimazu, Tadahiro, Barjau, Joaquin, Sohtome, Yoshihiro, Sodeoka, Mikiko, Shinkai, Yoichi. 2014. Selenium-based S-adenosylmethionine analog reveals the mammalian seven-beta-strand methyltransferase METTL10 to be an EF1A1 lysine methyltransferase. In PloS one, 9, e105394. doi:10.1371/journal.pone.0105394. https://pubmed.ncbi.nlm.nih.gov/25144183/

4. Jakobsson, Magnus E, Moen, Anders, Bousset, Luc, Melki, Ronald, Falnes, Pål Ø. 2013. Identification and characterization of a novel human methyltransferase modulating Hsp70 protein function through lysine methylation. In The Journal of biological chemistry, 288, 27752-63. doi:10.1074/jbc.M113.483248. https://pubmed.ncbi.nlm.nih.gov/23921388/