RNA-Guided RNA Pseudouridylation and 2’-O-Methylation

RNA-guided RNA modifications, including pseudouridylation and 2′-O-methylation, are naturally occurring processes that introduce pseudouridines (Ψ) and 2’-O-methylated residues (2’-O−Me) into various types of RNA. This modification is orchestrated by two distinct families of ribonucleoprotein complexes: Box H/ACA RNP and Box C/D RNP. Each complex comprises a unique guide (g)RNA (Box H/ACA gRNA or Box C/D gRNA) and a set of core proteins responsible for pseudouridylation and 2’-O-methylation, respectively. The specificity of these modifications is conferred by base-pairing of Box H/ACA gRNA and Box C/D gRNA with their RNA substrates. Here, we discuss the mechanism and function of RNA-guided pseudouridylation and 2’-O-methylation.