POLS National Science Centre Poland | EEA | Norway Grants

Structural and functional studies of human PNPase in mitochondrial RNA metabolism

Principal Investigator: Katarzyna Bandyra

Human polynucleotide phosphorylase (hPNPase) is a highly conserved exoribonuclease residing mostly in the mitochondrial intermembrane space, where its function is poorly understood. In bacteria, where the enzyme is best understood, PNPase can be re-programmed by the RNA chaperone Hfq and small regulatory RNA (sRNA) to switch from degradative to chaperoning roles in RNA-mediated gene regulation. As the human and bacterial enzymes are homologues, it is possible that hPNPase could have a dual mode of action as well, and could participate in diverse RNA-mediated regulatory processes once trapped in a non-degradative assembly. Our research will address what functions are played by hPNPase present in the intermembrane space of the human mitochondria. We will characterise the full-length enzyme and its capacity to bind substrates in the degradative and non-degradative modes, as well as identify potential hPNPase ternary complexes. In order to achieve these objectives, we will elucidate the structure-function relationship of hPNPase by cryo-EM.