The Might of MicroRNA in Mitochondria

Abstract

The mitochondrion is endowed with all the elements necessary for protein synthesis: it harbors its own genome—in the guise of a circular ≈16.5-kb chromosome—and transcription and translation apparatus. However, mitochondrial DNA (mtDNA) has just 37 genes, which encode 22 mitochondrial tRNAs, 2 mitochondrial rRNAs, and only 13 protein subunits belonging to respiratory complexes I, III, IV, and V1; all the subunits of complex II and the >1000 other proteins needed within the mitochondrion for its proper functioning are transcribed from nuclear genes, synthesized in the cytosol, and then transported into the organelle, where many are then posttranslationally processed before being located into position. The limited size of mtDNA also means that most of the machinery needed to regulate mitochondrial gene expression derives from nuclear genes.2 To date, the mechanisms underlying the coordinated expression of mitochondrial-encoded and nuclear gene–encoded transcripts remain to be fully elucidated. Article, see p 1596 The quintessential regulatory mechanisms of molecular biology are mediated by proteins, and a number of protein import mechanisms have been discovered for mitochondria.3 The contribution of regulatory noncoding (nc) RNAs to gene expression is a more recent discovery.4 Although mtDNA lacks introns and harbors only 2 (≈900 bp) regulatory regions for replication and transcription, several ncRNA candidates have been reported to be transcribed within mammalian mitochondria.5,6 Translocation into the mitochondrion of nuclear-derived RNAs—specifically of infrastructural tRNAs—was hypothesized to occur in the late 1960s, but this was not taken seriously for decades, and the mechanisms have remained more elusive.7 However, light is beginning to be shed on how ncRNAs are involved in the regulation of mitochondrial function, and with the discovery of microRNA (miRNA),8 studies may now be taking on a new impetus. In fact, apart from the presence in the cytosol of …