3methylcytosine

3-methylcytosine, commonly abbreviated as 3mC or m3C, is a term used for a methylated derivative of cytosine that appears in nucleic acids in two related contexts. In RNA, 3-methylcytidine is a natural post-transcriptional modification detected in various RNA species, including transfer RNA (tRNA) and ribosomal RNA (rRNA), and sometimes in messenger RNA (mRNA). In DNA, 3-methylcytosine refers to a methyl group added at the N3 position of cytosine (N3-methylcytosine), a type of alkylation lesion produced by exposure to certain chemical alkylating agents.

In DNA, 3-methylcytosine is considered a DNA damage product rather than a regulated epigenetic mark. It disrupts normal base pairing, impedes replication and transcription, and can contribute to mutagenesis if left unrepaired. Cellular repair mechanisms include base excision repair pathways and direct reversal by AlkB/ABH family demethylases that can remove methyl groups from m3C.

In RNA, 3-methylcytidine is a bona fide modification introduced by RNA methyltransferases at specific sites within tRNA, rRNA, and sometimes mRNA. The exact positions and enzymes vary among organisms. The presence of m3C in RNA can influence RNA structure, stability, and decoding properties, potentially affecting translation efficiency and fidelity. The biological roles of RNA m3C are an active area of research, with evidence linking it to proper tRNA folding and codon-anticodon interactions in some contexts.

Detection and analysis of 3mC rely on techniques such as mass spectrometry, chromatographic methods, and, for RNA, sequencing approaches that map modified nucleosides. Overall, 3mC represents a nucleic acid modification with distinct implications depending on whether it is a DNA lesion or a natural RNA modification.