Multi-Omics Analysis Unveils Nsun5-Mediated Molecular Alterations in the Somatosensory Cortex and Its Impact on Pain Sensation

Nsun5 assumes a pivotal role in the regulation of RNA methylation, and its deficiency has been linked to the advancement of hepatocellular carcinoma, gliomas, tetralogy of Fallot, cognitive deficits in Williams-Beuren syndrome, and brain development. This underscores Nsun5's significant involvement in the nervous system. In this study, we present evidence of Nsun5's influence on the structure of the primary somatosensory cortex. Through comprehensive multi-omics analyses, we unveil a spectrum of systematically altered genes and proteins, collectively engaged in the orchestration of translation, neurotransmitter metabolism, nerve conduction, synaptic transmission, and other functions. Notably, there are discernible changes in molecules associated with pain sensation, strongly indicating that Nsun5 deficiency undermines pain-related behavior. This study establishes a clear link between Nsun5 deficiency and transcriptional and proteomic changes, as well as neurotransmitter expression within the primary somatosensory cortex, and uncovers its novel role in impaired pain perception.