Many RNA molecules are posttranscriptionally modified. This means that specific positions in the RNA chain are chemically changed by enzymes, mostly adding extra chemical groups.
RNA modifications are most abundant in tRNA, where about 20% of the residues are modified. They stabilize the tRNA tertiary structure, increase the accuracy of recognition by proteins from the aaRS families that aminoacylate the tRNA, and they allow one anticodon to recognize more than one codon. Some modified positions like the dihydrouridine in the D-loop and pseudouridine in the P-loop are highly conserved. Modifications also occur in rRNA. Some methylations of specific positions of the active site of bacterial ribosomes have been shown to confer resistance to antibiotics targeting translation. Other types of RNA (group I introns, mRNA, snRNA) also are modified occasionally.
About half of the known modified nucleotides are methylated. Especially, methylation of the 2′OH-position is common, because it provides some protection against hydrolysis. Many other chemical types of modifications are known: aminoacylation, glycosylation, thiolation, and sometimes a nucleotide is even modified more than once (hypermodified nucleotides). To date, about 119 different nucleotide modifications are known, all of which are listed in the Modomics database (http://iimcb.genesilico.pl/modomics).
The enzymes that introduce modifications belong to a wide variety of families. Generally, each enzyme is specifically modifying only one or just a few positions in its RNA target. Therefore, it is not surprising that many different enzymes are required. It has been estimated, that up to 10% of the proteins in E.coli are methyltransferases – a part of which methylates DNA, not RNA, though.
Experimental determination of nucleotide modifications is difficult, because they cannot be detected by standard sequencing or in vitro transcription techniques. One method especially useful for identifying modified nucleotides is mass spectrometry.
(c) 2011 Kristian Rother
