RNA pseudouridylation: new insights into an old modification

Pseudouridine is the most abundant post-transcriptionally modified nucleotide in various stable RNAs of all organisms. Pseudouridine is derived from uridine via base-specific isomerization, resulting in an extra hydrogen-bond donor that distinguishes it from other nucleotides. In eukaryotes, uridine-to-pseudouridine isomerization is catalyzed primarily by box H/ACA RNPs, ribonucleoproteins that act as pseudouridylases. When introduced into RNA, pseudouridine contributes significantly to RNA-mediated cellular processes. It was recently discovered that pseudouridylation can be induced by stress, suggesting a regulatory role for pseudouridine. It has also been reported that pseudouridine can be artificially introduced into mRNA by box H/ACA RNPs and that such introduction can mediate nonsense-to-sense codon conversion, thus demonstrating a new means of generating coding or protein diversity.