Advances in RNA cytosine-5 methylation: detection, regulatory mechanisms, biological functions and links to cancer

As an important posttranscriptional modification of RNA, 5-methylcytosine (m(5)C) has attracted increasing interest recently, with accumulating evidence suggesting the involvement of RNA m(5)C modification in multiple cellular processes as well as tumorigenesis. Cooperatively, advances in m(5)C detection techniques have enabled transcriptome mapping of RNA methylation at single-nucleotide resolution, thus stimulating m(5)C-based investigations. In this review, we summarize currently available approaches for detecting m(5)C distribution in RNA as well as the advantages and disadvantages of these techniques. Moreover, we elucidate the regulatory mechanisms of RNA m(5)C modification by introducing the molecular structure, catalytic substrates, cellular distributions and biological functions of RNA m(5)C regulators. The functional consequences of m(5)C modification on mRNAs, tRNAs, rRNAs and other RNA species, including viral RNAs and vault RNAs, are also discussed. Finally, we review the role of RNA m(5)C modification in cancer pathogenesis and progression, in hopes of providing new insights into cancer treatment.