Mitochondrial RNA polyadenylation: Defining RNA fate through 3' end regulation

Polyadenylation is a conserved post-transcriptional RNA modification with fundamentally different consequences for RNA fate across biological systems. In bacteria, chloroplasts, and plant mitochondria, adenylation is generally associated with RNA turnover and degradation, whereas its role in metazoan mitochondria remains incompletely understood. In metazoa, polyadenylation is best known for generating complete UAA stop codons in a subset of mitochondrial mRNAs. However, this explanation does not fully account for the evolutionary conservation of the modification, its diverse RNA substrates, or the broad phenotypic consequences of disrupted polyadenylation. In this review, we re-examine RNA adenylation and propose that, in metazoan mitochondria, polyadenylation primarily establishes a permissive 3' end state that governs RNA maturation, stability, translational competence, and decay. This perspective provides a unifying explanation for the diverse functions attributed to mitochondrial polyadenylation.