Mechanisms and functions of RNA-guided RNA modification

Abstract

RNA-guided 2'-O-methylations and pseudouridylations occur in several different types of RNAs and in a wide range of organisms. Hundreds of the RNAs that guide these modifications have been identified, leading to breakthroughs in our understanding of the mechanisms of RNA-guided RNA modifications and, to some extent, the functions of 2'-O-methylated residues and pseudouridines. There are two classes of guide RNAs, namely box C/D and box H/ACA RNAs, which direct 2'-O-methylations and pseudouridylations, respectively. The guide RNAs function primarily by binding to complementary regions in the target RNAs. Cellular guide RNAs exist in RNA-protein complexes comprised of one guide RNA and a set of proteins that includes the modifying enzyme (2'-O-methylase or pseudouridylase). We are beginning to understand the basis for the importance of the RNA-guided modifications, which are well conserved and clustered in functionally important regions of RNAs. Recent reports indicate that modified nucleotides in rRNAs and spliceosomal snRNAs contribute to protein synthesis and premRNA splicing, respectively.