Nsun4, also known as NOP2/Sun RNA methyltransferase 4, is a key m(5)C methyltransferase. It is involved in multiple biological processes such as RNA methylation, which impacts RNA stability, translation, and localization. It is associated with pathways like mTOR signaling, adherens junction, and RNA degradation. NSUN4 is crucial for mitochondrial ribosomal biogenesis, methylating cytosine 911 in 12S rRNA and coordinating mitoribosomal assembly [3].

In disease-related research, conditional Nsun4 mouse knockouts have shown its essential role in mitochondrial translation [3]. In glioma, loss-and gain-of-function experiments revealed that NSUN4-mediated RNA 5-methylcytosine promotes the malignant progression by enhancing CDC42 mRNA stabilization [1]. In lung cancer, NSUN4-mediated m5C modification of circERI3 increases its nuclear export, promoting cancer development by altering mitochondrial energy metabolism [2]. In hepatocellular carcinoma, NSUN4 is upregulated and can serve as an independent prognostic factor, stimulating malignant progression [4]. In non-small cell lung cancer, NSUN4 facilitates the activity of oncogenic protein CDC20 by mediating m5C modification of CDC20 mRNA, promoting NSCLC development [5].

In conclusion, NSUN4 is vital for RNA methylation-related functions and mitochondrial ribosomal biogenesis. Model-based research, especially KO/CKO mouse models, has revealed its significant contributions to the development of various cancers including glioma, lung cancer, and hepatocellular carcinoma, providing potential targets for cancer treatment.