FIG. 1.

Mechanism of RNA editing. (A) A cycle of U deletion or U insertion involves gRNA-directed cleavage of the pre-mRNA (open arrowhead), either 3′-U-exo or TUTase acting on the upstream fragment, and RNA ligase rejoining (4, 9, 22, 34). The two kinds of editing use distinct cleavage activities (10), and the 3′-U-exo is not a reverse TUTase reaction (9, 29), as indicated (≠). R = purine(s); Y = pyrimidine(s). The gRNA forms anchor and tether duplexes with pre-mRNA (indicated by base pairing), and its central guiding region becomes complementary upon accurate editing (4, 5). Dotted lines indicate that upon complete U removal or U addition, one or more base pairs could align the mRNA fragments, providing a “ligation bridge” (34). (B) The three steps in the action of an RNA ligase enzyme (E).