Figure 1. General mechanism of self-cleavage by the natural small ribozymes.

(A) A Brønsted-Lowry base (β) abstracts a proton to activate the 2′-OH nucleophile, which then attacks the adjacent phosphate, forming a pentacoordinate transition state (B) with approximate collinearity between the 2′-oxygen, phosphorus atom, and 5′-oxygen leaving group – the in-line attack geometry. The negative charge of the transition state may be stabilized by one or several metal cations (Mⁿ⁺) that interact through inner- or outer-sphere contacts with the non-bridging oxygen atoms or by long-distance coulombic stabilization. A Brønsted-Lowry acid (α) donates a proton to the 5′-oxygen leaving group, resulting in a 5′-product bearing a 2′,3′-cyclic phosphate and a 3′-product bearing a 5′-OH (C).