The precursor primer RNA for mammalian mitochondrial DNA leading-strand 
replication remains as a persistent R loop formed during transcription through 
the mitochondrial DNA control region. We have examined model R loops, which 
exist in a novel and physiologically accurate preprimer conformation, as 
potential substrates for mammalian RNase mitochondrial RNA processing (MRP). 
Mouse RNase MRP accurately cleaves an R loop containing the mouse mitochondrial 
DNA origin. The multiple cleavage sites on the R-loop substrate match the 
priming sites observed in vivo, suggesting that RNase MRP alone is capable of 
generating virtually all of the leading-strand replication primers.