Most mitochondrial mRNAs in kinetoplastid protozoa require post-transcriptional RNA editing that inserts and deletes uridylates, a process that is catalyzed by multiprotein editosomes. KREPA6 is the smallest of six editosome proteins that have predicted oligonucleotide-binding (OB) folds. Inactivation of KREPA6 expression results in disruption and ultimate loss of approximately 20S editosomes and inhibition of procyclic form cell growth. Gel shift studies show that recombinant KREPA6 binds RNA, but not DNA, with a preference for oligo-(U) whether on the 3' end of gRNA or as a (UU)(12) homopolymer. Thus, KREPA6 is essential for the structural integrity and presence of approximately 20S editosomes and for cell viability. It functions in RNA binding perhaps primarily through the gRNA 3' oligo(U) tail. The significance of these findings to key steps in editing is discussed.