<p>RNA (C5-cytosine) methyltransferases (RCMTs) catalyse the transfer of a methyl group to the 5th carbon of a cytosine base in RNA sequences to produce C5-methylcytosine. RCMTs use the cofactor S-adenosyl-L-methionine (SAM) as a methyl donor [<cite idref="PUB00054125"/>]. The catalytic mechanism of RCMTs involves an attack by the thiolate of a Cys residue on position 6 of the target cytosine base to form a covalent link, thereby activating C5 for methyl-group transfer. Following the addition of the methyl group, a second Cys residue acts as a general base in the beta-elimination of the proton from the methylated cytosine ring. The free enzyme is restored and the methylated product is released [<cite idref="PUB00054126"/>].</p> <p>Numerous putative RCMTs have been identified in archaea, bacteria and eukaryota [<cite idref="PUB00014205"/>, <cite idref="PUB00054127"/>]; most are predicted to be nuclear or nucleolar proteins [<cite idref="PUB00054128"/>]. The Escherichia coli Ribosomal RNA Small-subunit Methyltransferase Beta (RSMB) FMU (FirMicUtes) represents the first protein identified and characterised as a cytosine-specific RNA methyltransferase. RSMB was reported to catalyse the formation of C5-methylcytosine at position 967 of 16S rRNA [<cite idref="PUB00054129"/>, <cite idref="PUB00014203"/>].</p> <p>A classification of RCMTs has been proposed on the basis of sequence similarity [<cite idref="PUB00014205"/>]. According to this classification, RCMTs are divided into 8 distinct subfamilies [<cite idref="PUB00014205"/>]. Recently, a new RCMT subfamily, termed RCMT9, was identified [<cite idref="PUB00054127"/>]. Members of the RCMT contain a core domain, responsible for the cytosine-specific RNA methyltransferase activity. This 'catalytic' domain adopts the Rossmann fold for the accommodation of the cofactor SAM [<cite idref="PUB00054130"/>]. The RCMT subfamilies are also distinguished by N-terminal and C-terminal extensions, variable both in size and sequence [<cite idref="PUB00014205"/>].</p> RNA (C5-cytosine) methyltransferase