RNPS1 stabilizes NAT10 protein to facilitate translation in cancer via tRNA ac4C modification
Xiaochen Wang, Rongsong Ling, Yurong Peng, Weiqiong Qiu, Demeng Chen
Abstract
Abstract Existing studies have underscored the pivotal role of N-acetyltransferase 10 (NAT10) in various cancers. However, the outcomes of protein-protein interactions between NAT10 and its protein partners in head and neck squamous cell carcinoma (HNSCC) remain unexplored. In this study, we identified a significant upregulation of RNA-binding protein with serine-rich domain 1 (RNPS1) in HNSCC, where RNPS1 inhibits the ubiquitination degradation of NAT10 by E3 ubiquitin ligase, zinc finger SWIM domain-containing protein 6 (ZSWIM6), through direct protein interaction, thereby promoting high NAT10 expression in HNSCC. This upregulated NAT10 stability mediates the enhancement of specific tRNA ac 4 C modifications, subsequently boosting the translation process of genes involved in pathways such as IL-6 signaling, IL-8 signaling, and PTEN signaling that play roles in regulating HNSCC malignant progression, ultimately influencing the survival and prognosis of HNSCC patients. Additionally, we pioneered the development of TRMC-seq, leading to the discovery of novel tRNA-ac 4 C modification sites, thereby providing a potent sequencing tool for tRNA-ac 4 C research. Our findings expand the repertoire of tRNA ac 4 C modifications and identify a role of tRNA ac 4 C in the regulation of mRNA translation in HNSCC.