Abstract

tRNA nucleotidyltransferase adds the invariant CCA‐terminus to the tRNA 3′‐end, a central step in tRNA maturation. This CCA‐adding enzyme is a specialized RNA polymerase that synthesizes the CCA sequence at high fidelity in all kingdoms of life. Recently, an additional function of this enzyme was identified, where it generates a specific degradation tag on structurally unstable tRNAs. This tag consists of an additional repeat of the CCA triplet, leading to a 3′‐terminal CCACCA sequence. In order to explain how the enzyme catalyzes this extended polymerization reaction, Kuhn et al. solved a series of co‐crystal structures of the CCA‐adding enzyme from Archaeoglobus fulgidus in complex with different tRNA substrates. They show that the enzyme forces a bound unstable tRNA to refold the acceptor stem for a second round of CCA‐addition, while stable transcripts are robust enough to resist this isomerization. In this review, we discuss how the CCA‐adding enzyme uses a simple yet very elegant way to scrutinize its substrates for sufficient structural stability and, consequently, functionality.