Abstract
Almost 60 years ago, Severo Ochoa was awarded the Nobel Prize in Physiology or Medicine for his discovery of the enzymatic synthesis of RNA by polynucleotide phosphorylase (PNPase). Although this discovery provided an important tool for deciphering the genetic code, subsequent work revealed that the predominant function of PNPase in bacteria and eukaryotes is catalyzing the reverse reaction, i.e., the release of ribonucleotides from RNA. PNPase has a crucial role in RNA metabolism in bacteria and eukaryotes mainly through its roles in processing and degrading RNAs, but additional functions in RNA metabolism have recently been reported for this enzyme. Here, we discuss these established and noncanonical functions for PNPase and the possibility that the major impact of PNPase on cell physiology is through its unorthodox roles.
Highlights
Author summaryDistributed among bacteria and eukaryotes, including humans, polynucleotide phosphorylase (PNPase) is a critical enzyme in RNA metabolism that functions in most organisms as a 30 to 50 exoribonuclease
In 1955, Grunberg-Manago and Ochoa reported that the enzyme polynucleotide phosphorylase (PNPase) from the gram-negative bacterium Azobacter vinelandii synthesized polynucleotides from nucleotide diphosphates and catalyzed the reverse reaction, the phosphorolysis of polynucleotides [1, 2]
Both RNases serve critical roles in mitochondria, in which RNase MRP cleaves the RNA primers used for mitochondrial DNA replication and RNase P processes the large mitochondrial polycistronic transcripts that give rise to 22 tRNAs, 12S and 16S rRNAs, as well as 13 mRNAs encoding electron transport chain (ETC) components involved in oxidative phosphorylation, i.e., the synthesis of ATP that is powered by the transfer of electrons from NADH or FADH2 to O2
Summary
Distributed among bacteria and eukaryotes, including humans, polynucleotide phosphorylase (PNPase) is a critical enzyme in RNA metabolism that functions in most organisms as a 30 to 50 exoribonuclease. Inactivation of the gene encoding PNPase results in a wide range of consequences, including impaired growth, diminished stress responses, and loss of virulence. PNPase has an essential role in mitochondrial function. Mutations in the gene encoding the human PNPase (hPNPase) that reduce its activity can lead to hereditary hearing loss, encephalomyopathy, severe axonal neuropathy, delayed myelination, and Leigh syndrome. We examine its role in bacterial mRNA and rRNA decay, RNA processing, and small regulatory RNA (sRNA) degradation and stabilization. We explore the recently reported findings on the function of hPNPase in mitochondrial RNA import and degradation and cytoplasmic mRNA and noncoding RNA decay.
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