Post-transcriptional regulation by cytosine-5 methylation of RNA

The recent advent of high-throughput sequencing technologies coupled with RNA modifications detection methods has allowed the detection of RNA modifications at single nucleotide resolution giving a more comprehensive landscape of post-transcriptional gene regulation pathways. In this review, we focus on the occurrence of 5-methylcytosine (m⁵C) in the transcriptome. We summarise the main findings of the molecular role in post-transcriptional regulation that governs m⁵C deposition in RNAs. Functionally, m⁵C deposition can regulate several cellular and physiological processes including development, differentiation and survival to stress stimuli. Despite many aspects concerning m⁵C deposition in RNA, such as position or sequence context and the fact that many readers and erasers still remain elusive, the overall recent findings indicate that RNA cytosine methylation is a powerful mechanism to post-transcriptionally regulate physiological processes. In addition, mutations in RNA cytosine-5 methyltransferases are associated to pathological processes ranging from neurological syndromes to cancer.