RNA m5C modification: from physiology to pathology and its biological significance

Abstract

RNA 5-methylcytosine (m5C) modification is a crucial epitranscriptomic mark that regulates RNA stability, processing, and translation. Emerging evidence highlights its essential role in various physiological processes, including cellular differentiation, stem cell maintenance, and immune responses. Dysregulation of m5C modification has been implicated in multiple pathological conditions, particularly in cancer, neurodegenerative disorders, and metabolic diseases. This review provides a comprehensive overview of the molecular mechanisms governing m5C deposition, its functional consequences in normal physiology, and its contributions to disease pathogenesis. Furthermore, we discuss the potential of m5C as a biomarker and therapeutic target, offering new insights into its biological significance and clinical relevance.

Keywords: 5-methylcytosine; biological significance; cancer immunotherapy; methods; pathology; physiology.

Figure 1

RNA m5C modification is a dynamic process. RNA m5C modification (5-methylcytosine modification) refers to the chemical modification where the cytosine residues in RNA molecules are methylated at the carbon 5 position. This modification is widely present in various types of RNA, including messenger RNA (mRNA), ribosomal RNA (rRNA), transfer RNA (tRNA), and non-coding RNA (ncRNA). RNA m5C modification plays a crucial role in various biological processes.

Figure 2

The role and mechanisms of RNA m5C modification in the regulation of the tumor microenvironment. NUSUN2 mediates m5C modifications of various downstream target genes, recruits the YBX1 reader protein, and subsequently regulates the RNA stability of these target genes, upregulating their expression. This plays a key role in tumor immune microenvironment remodeling, including M2 macrophage polarization, the formation of an immunosuppressive microenvironment, and CD8+ cell activation.