RNA editing by nucleotide insertion and deletion. (a) Before editing, a pre-mRNA is missing some U residues required in the mature RNA and contains some extra U residues. A guide RNA (gRNA) in the editosome base-pairs with the pre-mRNA, guiding insertion and deletion of U residues. The insertions and deletions change the protein sequence encoded by the mRNA. (b) The editosome has several enzymatic activities: a nuclease to cleave the pre-mRNA at an insertion site, TUTase to fill in missing U residues, exoribonuclease to delete extra U residues, and ligase to seal the nicks.