University of California Research Initiatives

Kinetoplastid RNA (kRNA) editing is a process that creates translatable mitochondrial mRNA transcripts from cryptogene encoded RNAs and is unique for kinetoplastids, such as Trypanosoma brucei. In addition to the catalytic 20S editosome, multiple accessory proteins are required for this conversion. Recently, the multiprotein mitochondrial RNA binding complex 1 (MRB1) has emerged as a key player in this process. MRB1 consists of six core proteins but makes dynamic interactions with additional accessory proteins. Here we describe the characterization of one such factor, the 72 kDa MRB1590 protein. In vivo experiments indicate a role for MRB1590 in editing mitochondrial mRNA transcripts, in particular the transcript encoding the ATP synthase subunit 6 (A6). Structural studies show that MRB1590 is dimeric and contains a central ABC-ATPase fold embedded between novel N- and C-terminal regions. The N-terminal domains combine to create a basic pore and biochemical studies indicate residues in this region participate in RNA binding. Structures capturing distinct MRB1590 conformations reveal that the RNA binding pore adopts closed and open states, with the latter able to accommodate RNA. Based on these findings, implications for MRB1590 function are discussed.