Cleavage of non‐tRNA substrates by eukaryal tRNA splicing endonucleases

Abstract
Eukaryal tRNA splicing endonucleases use the mature domains of pre‐tRNAs as their primary recognition elements. However, they can also cleave in a mode that is independent of the mature domain, when substrates are able to form the bulge–helix–bulge structure (BHB), which is cleaved by archaeal tRNA endonucleases. We present evidence that the eukaryal enzymes cleave their substrates after forming a structure that resembles the BHB. Consequently, these enzymes can cleave substrates that lack the mature domain altogether. That raises the possibility that these enzymes could also cleave non‐tRNA substrates that already have a BHB. As predicted, they can do so, both in vitro and in vivo.