2Omethylations

2'-O-methylation, often written as 2'-O-Me, is the covalent modification of RNA in which a methyl group is attached to the 2'-hydroxyl group of the ribose sugar. The modification occurs at numerous sites in cellular RNAs, most prominently in ribosomal RNA (rRNA) and small nucleolar RNA (snoRNA) guides, as well as in transfer RNA (tRNA).

Biological context: In eukaryotes, many 2'-O-methylations in rRNA are installed by box C/D snoRNPs, with fibrillarin acting as the catalytic methyltransferase, guided by snoRNA to specific sites. In bacteria and archaea, 2'-O-methylations are introduced by dedicated methyltransferases, such as members of the FtsJ/RrmJ family; some tRNA and rRNA positions are modified by multiple enzymes. The modifications influence RNA folding, stability, and interactions with proteins, and are often essential for ribosome assembly and function.

Detection and applications: Mapping 2'-O-methylation sites in RNA is achieved by methods such as RiboMethSeq, RTL-P, and mass spectrometry. In biotechnology, synthetic 2'-O-methyl RNA oligonucleotides are widely used because the modification increases resistance to nucleases and reduces immunostimulation; these modified nucleotides are common in antisense oligonucleotides, siRNA, and other therapeutic modalities.

Impact: The pattern of 2'-O-methylations varies across organisms and tissues and can change in disease states, potentially affecting gene expression and ribosome performance. Ongoing research investigates their roles in development, immune recognition, and cellular stress responses.