Chtop-KO Mouse

Chtop, short for Chromatin target of protein arginine methyltransferase, is a versatile regulator involved in gene-specific transcription and mRNA export. It binds competitively to arginine methyltransferases PRMT1 and PRMT5, promoting asymmetric or symmetric methylation of arginine residues respectively. Chtop is part of the TREX complex, linking transcription elongation to mRNA export, and is crucial for the expression of certain gene groups and in the pathogenesis of some diseases [1,4].

In chemoresistant epithelial ovarian cancer (EOC), Chtop is highly expressed, and its knockdown enhances cisplatin-induced apoptosis, reduces cell stemness, and decreases metastatic potential, suggesting it as a potential therapeutic target [2]. In microglia, LPS stimulation induces Chtop expression. Knocking down Chtop decreases pro-inflammatory cytokine expression, alters cell metabolism, and alleviates microglia-mediated neuroinflammation [3]. Chtop also auto-regulates its expression level via intron retention and nonsense-mediated decay of its own mRNA [5].

In conclusion, Chtop is essential in regulating gene-specific expression, mRNA export, and cell-specific functions. Its study in models provides insights into diseases like chemoresistant EOC and microglia-mediated neuroinflammation, highlighting its potential as a therapeutic target in these disease areas.

References:

1. Izumikawa, Keiichi, Ishikawa, Hideaki, Simpson, Richard J, Takahashi, Nobuhiro. 2018. Modulating the expression of Chtop, a versatile regulator of gene-specific transcription and mRNA export. In RNA biology, 15, 849-855. doi:10.1080/15476286.2018.1465795. https://pubmed.ncbi.nlm.nih.gov/29683372/

2. Feng, Xiaojie, Bai, Xupeng, Ni, Jie, Graham, Peter, Li, Yong. 2019. CHTOP in Chemoresistant Epithelial Ovarian Cancer: A Novel and Potential Therapeutic Target. In Frontiers in oncology, 9, 557. doi:10.3389/fonc.2019.00557. https://pubmed.ncbi.nlm.nih.gov/31380263/

3. Zhou, Xin, Lv, Mengfei, Duan, Zhongying, Liu, Jiake, Cui, Yu. . CHTOP Promotes Microglia-Mediated Inflammation by Regulating Cell Metabolism and Inflammatory Gene Expression. In Journal of immunology (Baltimore, Md. : 1950), 212, 677-688. doi:10.4049/jimmunol.2300572. https://pubmed.ncbi.nlm.nih.gov/38117276/

4. Chang, Chung-Te, Hautbergue, Guillaume M, Walsh, Matthew J, Philipsen, Sjaak, Wilson, Stuart A. 2013. Chtop is a component of the dynamic TREX mRNA export complex. In The EMBO journal, 32, 473-86. doi:10.1038/emboj.2012.342. https://pubmed.ncbi.nlm.nih.gov/23299939/

5. Izumikawa, Keiichi, Yoshikawa, Harunori, Ishikawa, Hideaki, Isobe, Toshiaki, Takahashi, Nobuhiro. 2016. Chtop (Chromatin target of Prmt1) auto-regulates its expression level via intron retention and nonsense-mediated decay of its own mRNA. In Nucleic acids research, 44, 9847-9859. doi:. https://pubmed.ncbi.nlm.nih.gov/27683223/