Human polynucleotide phosphorylase in mitochondrial RNA metabolism

Ever since its discovery more than 70 years ago, the enzyme polynucleotide phosphorylase (PNPase) has been the subject of intensive research that has highlighted its key functional roles. The enzyme was first described in 1955 for its ability to synthesise RNA from nucleoside diphosphates. This discovery led to a Nobel Prize in Physiology or Medicine in 1959 for using PNPase to synthesise artificial RNA. However, it soon became evident that the primary function of this enzyme, conserved across diverse species, is 3'-5' RNA phosphorolysis rather than polymerisation. Remarkably, over 60 years later, it was discovered that PNPase has an even broader range of functions as it was shown to act as a conditional RNA chaperone in bacteria. In humans, PNPase (hPNPase) is located in mitochondria, where it plays a role in mitochondrial RNA (mtRNA) metabolism, thereby regulating mitochondrial function and the overall cell fitness. In this review, we present the current scope of knowledge of hPNPase, including its structure, subcellular localisation, metabolic activity, roles in mtRNA transport, processing and degradation, and its involvement in apoptosis.