Polynucleotide phosphorylase activity may be modulated by metabolites in XXXX .

@entity1792 @entity526
RNA turnover is an essential element of cellular homeostasis and response to environmental change. Whether the ribonucleases that mediate RNA turnover can respond to cellular metabolic status is an unresolved question. Here we present evidence that the Krebs cycle metabolite @entity1792 affects the activity of @entity526 polynucleotide phosphorylase (PNPase) and, conversely, that cellular metabolism is affected widely by PNPase activity. An @entity526 that requires PNPase for viability has suppressed growth in the presence of increased @entity1792 concentration. Transcriptome analysis reveals a PNPase-mediated response to @entity1792 , and PNPase deletion broadly impacts on the metabolome. In vitro, @entity1792 directly binds and modulates PNPase activity, as predicted by crystallographic data. Binding of metal-chelated @entity1792 in the active site at physiological concentrations appears to inhibit enzyme activity. However, metal-free @entity1792 is bound at a vestigial active site, where it stimulates PNPase activity. Mutagenesis data confirmed a potential role of this vestigial site as an allosteric binding pocket that recognizes metal-free @entity1792 . Collectively, these findings suggest that RNA degradative pathways communicate with central metabolism. This communication appears to be part of a feedback network that may contribute to global regulation of metabolism and cellular energy efficiency.
