The detection and manipulation of RNA is greatly aided by chemical modification. Therefore, there is tremendous interest in novel methods to site-specifically associate RNA with small molecules such as imaging probes and affinity labels. Conventional methodologies for detecting RNA include the use of antisense probes, aptamers, and fusion proteins that recognize specific RNA secondary structures. Relatively less explored are the use of enzymatic reactions for site-specific RNA labeling. Notably, these past approaches have not demonstrated the ability to append large functional molecules directly onto the RNA of interest. Instead they typically rely upon small bio-orthogonal handles, which after undergoing a second chemical reaction, can be modified by functional probes such as fluorophores or affinity ligands. An ideal enzymatic reaction for labeling RNA would involve recognition of a minimal RNA structural motif, result in irreversible covalent modification, and would be capable of directly incorporating a diverse array of functional molecules such as fluorophores, affinity ligands, etc. in a single step.