Unique 2′-O-Methylation by Hen1 in Eukaryotic RNA Interference and Bacterial RNA Repair

In an RNA transcript, the 2'-OH group at the 3'-terminal nucleotide is unique as it is the only 2'-OH group that is adjacent to a 3'-OH group instead of a phosphate backbone. The 2'-OH group at the 3'-terminal nucleotide of certain RNAs is methylated in vivo, which is acheived by a methyltransferase named Hen1 that is mechanistically distinct from other known RNA 2'-O-methyltransferases. In eukaryotic organisms, 3'-terminal 2'-O-methylation of small RNAs stabilizes these small RNAs for RNA interference (RNAi). In bacteria, the same methylation during RNA repair results in repaired RNA resisting future damage at the site of repair. Although the chemistry performed by the eukaryotic and bacterial Hen1 is the same, the mechanisms of how RNA is stabilized as a result of the 3'-terminal 2'-O-methylation are different between the eukaryotic RNAi and the bacterial RNA repair. In this review, I will discuss the distribution of Hen1 in living organisms, the classification of Hen1 into four subfamilies, the structure and mechanism of Hen1 that allows it to conduct RNA 3'-terminal 2'-O-methylation, and the possible evolutionary origin of Hen1 present in bacterial and eukaryotic organisms.