E. coli YhbY belongs to a conserved family of hypothetical proteins represented in eubacteria, archaea, and plants (Pfam code UPF0044). Three maize proteins harboring UPF0044-like domains are required for chloroplast group II intron splicing, and bioinformatic data suggest a role for prokaryotic UPF0044 members in translation. The crystal structure of YhbY has been determined. YhbY has a fold similar to that of the C-terminal domain of translation initiation factor 3 (IF3C), which binds to 16S rRNA in the 30S ribosome. Modeling studies indicate that the same surface is highly basic in all members of UPF0044, suggesting a conserved RNA binding surface. Taken together, the evidence suggests that members of UPF0044 constitute a previously unrecognized class of RNA binding domain.