Hnrnpa2b1, or heterogeneous nuclear ribonucleoprotein A2/B1, is an RNA-binding protein and a reader of N6-methyladenosine (m6A) modification. It is involved in multiple RNA-related processes such as alternative splicing, primary miRNA processing, and nucleocytoplasmic trafficking of mRNAs [3]. It also participates in crucial biological pathways, including innate immune response and tumor-related signaling, thus being of great biological importance. Genetic models, like KO mouse models, have been instrumental in studying its functions.

Knockout of Hnrnpa2b1 in mice leads to Sertoli cell-only syndrome (SCOS), causing complete male infertility, revealing its essential role in male fertility [2]. In multiple myeloma, depletion of HNRNPA2B1 in MM cells inhibits cell proliferation and induces apoptosis, suggesting its role in promoting tumor progression [1]. In hepatocellular carcinoma, knockout of hnRNPA2B1 reduces cell proliferation, migration, and invasion in vitro and inhibits tumor formation in vivo, indicating its role in promoting tumorigenesis [4].

In summary, Hnrnpa2b1 plays essential roles in male fertility and is involved in the progression of multiple myeloma and hepatocellular carcinoma. Gene knockout studies in mouse models have been crucial in revealing these functions, providing insights into the underlying mechanisms of these biological processes and diseases, which may help in developing targeted therapeutic strategies.

References:

1. Jiang, Fengjie, Tang, Xiaozhu, Tang, Chao, Gu, Chunyan, Yang, Ye. 2021. HNRNPA2B1 promotes multiple myeloma progression by increasing AKT3 expression via m6A-dependent stabilization of ILF3 mRNA. In Journal of hematology & oncology, 14, 54. doi:10.1186/s13045-021-01066-6. https://pubmed.ncbi.nlm.nih.gov/33794982/

2. Wang, Xiaoli, Fan, Xu, Zhang, Jin, Zhang, Youzhi, Yuan, Shuiqiao. 2024. hnRNPA2B1 represses the disassembly of arsenite-induced stress granules and is essential for male fertility. In Cell reports, 43, 113769. doi:10.1016/j.celrep.2024.113769. https://pubmed.ncbi.nlm.nih.gov/38363675/

3. Alarcón, Claudio R, Goodarzi, Hani, Lee, Hyeseung, Tavazoie, Saeed, Tavazoie, Sohail F. 2015. HNRNPA2B1 Is a Mediator of m(6)A-Dependent Nuclear RNA Processing Events. In Cell, 162, 1299-308. doi:10.1016/j.cell.2015.08.011. https://pubmed.ncbi.nlm.nih.gov/26321680/

4. Hao, Weijie, Chen, Zhimin, Tang, Jingzhi, Gao, Wei-Qiang, Xu, Huiming. 2023. hnRNPA2B1 promotes the occurrence and progression of hepatocellular carcinoma by downregulating PCK1 mRNA via a m6A RNA methylation manner. In Journal of translational medicine, 21, 861. doi:10.1186/s12967-023-04704-4. https://pubmed.ncbi.nlm.nih.gov/38017546/