Rbm46, an RNA-binding protein, is essential for gametogenesis and has key functions in regulating gene expression at the post-transcriptional level. It is involved in pathways related to meiosis entry during spermatogenesis, as well as embryonic development and RNA editing [1,2,3]. Genetic models, such as knockout mice, have been crucial for studying its functions [1,2,4,5,6,7,8].

In mice, testis-specific Rbm46 knockout leads to infertility due to defective mitotic-to-meiotic transition, phenocopying global Ythdc2 or Meioc knockout. RBM46 binds to 3' UTR of mitotic transcripts near YTHDC2 U-rich motifs and targets them for degradation, regulating meiosis entry in spermatogenesis [1]. In Rbm46 knockout mice, meiotic cohesin subunits have reduced translation despite unaltered mRNA levels, resulting in synaptonemal complex formation defects and meiotic arrest [2]. Zebrafish rbm46 mutants show masculinization and infertility, with impaired spermatogenesis and absent meiosis events [4]. In mouse embryonic stem cells, Rbm46 knockout leads to elevated reactive oxygen species due to diminished mitochondrial autophagy [5].

In summary, Rbm46 is vital for gametogenesis, especially in regulating the mitotic-to-meiotic transition during spermatogenesis. The use of Rbm46 knockout mouse models has provided insights into meiosis-related fertility disorders, as dysregulated RBM46 expression is associated with human male fertility disorders [1].

References:

1. Qian, Baomei, Li, Yang, Yan, Ruoyu, Zhou, Jian, Ye, Lan. 2022. RNA binding protein RBM46 regulates mitotic-to-meiotic transition in spermatogenesis. In Science advances, 8, eabq2945. doi:10.1126/sciadv.abq2945. https://pubmed.ncbi.nlm.nih.gov/36001654/

2. Lv, Yue, Lu, Gang, Cai, Yuling, Liu, Hongbin, Chan, Wai-Yee. 2022. RBM46 is essential for gametogenesis and functions in post-transcriptional roles affecting meiotic cohesin subunits. In Protein & cell, 14, 51-63. doi:10.1093/procel/pwac040. https://pubmed.ncbi.nlm.nih.gov/36726756/

3. Wang, Shanshan, Kim, Kyumin, Gelvez, Nicolas, Vermulst, Marc, Chen, Xiaojiang S. 2023. Identification of RBM46 as a novel APOBEC1 cofactor for C-to-U RNA-editing activity. In Journal of molecular biology, 435, 168333. doi:10.1016/j.jmb.2023.168333. https://pubmed.ncbi.nlm.nih.gov/38708190/

4. Dai, Xiangyan, Cheng, Xinkai, Huang, Jianfei, Wang, Zhijian, Yin, Zhan. . Rbm46, a novel germ cell-specific factor, modulates meiotic progression and spermatogenesis. In Biology of reproduction, 104, 1139-1153. doi:10.1093/biolre/ioab016. https://pubmed.ncbi.nlm.nih.gov/33524105/

5. Zhong, Jinchen, Xu, Jing, Chen, Xiaoyang, Zhou, Zhi, Li, Lingsong. 2024. Rbm46 inhibits reactive oxygen species in mouse embryonic stem cells through modulating BNIP3-mediated mitophagy. In Biochemical and biophysical research communications, 708, 149779. doi:10.1016/j.bbrc.2024.149779. https://pubmed.ncbi.nlm.nih.gov/38518724/

6. Wang, Chenchen, Chen, Yuanfan, Deng, Hongkui, Gao, Shaorong, Li, Lingsong. 2014. Rbm46 regulates trophectoderm differentiation by stabilizing Cdx2 mRNA in early mouse embryos. In Stem cells and development, 24, 904-15. doi:10.1089/scd.2014.0323. https://pubmed.ncbi.nlm.nih.gov/25397698/

7. Zhai, Lei, Wang, Chenchen, Chen, Yuanfan, Zhou, Shixin, Li, Lingsong. 2017. Rbm46 regulates mouse embryonic stem cell differentiation by targeting β-Catenin mRNA for degradation. In PloS one, 12, e0172420. doi:10.1371/journal.pone.0172420. https://pubmed.ncbi.nlm.nih.gov/28212427/

8. Peart, Natoya J, Johnson, Taylor A, Lee, Sungkyoung, Geyer, Christopher B, Carstens, Russ P. 2022. The germ cell-specific RNA binding protein RBM46 is essential for spermatogonial differentiation in mice. In PLoS genetics, 18, e1010416. doi:10.1371/journal.pgen.1010416. https://pubmed.ncbi.nlm.nih.gov/36129965/