Mitochondrially mediated RNA interference, a retrograde signaling system affecting nuclear gene expression

Several functional classes of short noncoding RNAs are involved in manifold regulatory processes in eukaryotes, including, among the best characterized, miRNAs. One of the most intriguing regulatory networks in the eukaryotic cell is the mito-nuclear crosstalk: recently, miRNA-like elements of mitochondrial origin, called smithRNAs, were detected in a bivalve species, Ruditapes philippinarum. These RNA molecules originate in the organelle but were shown in vivo to regulate nuclear genes. Since miRNA genes evolve easily de novo with respect to protein-coding genes, in the present work we estimate the probability with which a newly arisen smithRNA finds a suitable target in the nuclear transcriptome. Simulations with transcriptomes of 12 bivalve species suggest that this probability is high and not species specific: one in a hundred million (1 × 10^-8) if five mismatches between the smithRNA and the 3' mRNA are allowed, yet many more are allowed in animals. We propose that novel smithRNAs may easily evolve as exaptation of the pre-existing mitochondrial RNAs. In turn, the ability of evolving novel smithRNAs may have played a pivotal role in mito-nuclear interactions during animal evolution, including the intriguing possibility of acting as speciation trigger.