Polyribonucleotide nucleotidyltransferase 1 (PNPT1) (PNPT1)

Polyribonucleotide nucleotidyltransferase 1 (PNPT1), also known as PNPase, is a mitochondrial enzyme primarily responsible for the processing and degradation of mitochondrial RNA (mtRNA) and the translocation of small RNAs into the mitochondria (UniProt Q8TCS8). It resides in the mitochondrial intermembrane space and matrix, playing a pivotal role in maintaining mitochondrial homeostasis and respiratory chain function (NCBI Gene ID: 8717). Mutations in the PNPT1 gene are associated with severe pathologies, including combined oxidative phosphorylation deficiency 13 (COXPD13) and autosomal recessive nonsyndromic deafness 70 (PubMed: 22901948). Recent studies have identified PNPT1 as a key regulator of the innate immune response; its deficiency leads to the accumulation and leakage of mitochondrial double-stranded RNA (dsRNA) into the cytoplasm, which triggers the MDA5-mediated interferon-beta signaling pathway (Dhir et al., 2018, Nature). While no small-molecule inhibitors are currently approved for clinical use, PNPT1 mRNA is a target of interest for RNA-based therapeutics, such as antisense oligonucleotides (ASOs) and siRNA, particularly for modulating immune responses or investigating its role in cancer cell growth (PubMed: 15647280).

Other names

PNPaseOld-35Polynucleotide phosphorylase 1COXPD13PNPASE

Antisense inhibition or RNA interference to modulate protein expression levels