The FASTK protein family: exploring non-canonical mitochondrial RNA processing

Mitochondrial gene expression is essential for oxidative phosphorylation. Transcription of the human circular mitochondrial DNA initiates at two distinct divergent promoters, one on each strand, leading to two almost genome-length polycistronic transcripts. Therefore, the expression level of each gene is mainly controlled through post-transcriptional events. RNA processing triggers the post-transcriptional maturation. As most mRNAs and rRNAs within the polycistronic transcripts are flanked by tRNAs, cleaving off these tRNA junctions releases individual transcripts. However, this ‘tRNA punctuation model’ does not explain the processing of mRNAs that lack flanking tRNAs, and the molecular mechanisms underlying this non-canonical RNA processing remain unknown. To answer this long-standing question, we exploited the role of the FASTK family proteins: emerging key mitochondrial post-transcriptional regulators. Here, we propose that the FASTK proteins regulate the expression of a broad range of mitochondrial transcripts, including poorly investigated non-coding RNAs, by fine-tuning the processing of canonical and non-canonical RNA junctions.