Inhibition of homologous phosphorolytic ribonucleases by citrate may represent an evolutionarily conserved communicative link between RNA degradation and central metabolism.

Autor:	Stone CM; School of Biological Sciences and Institute of Biomedical and Biomolecular Sciences, University of Portsmouth, Portsmouth, PO1 2DY, UK., Butt LE; School of Biological Sciences and Institute of Biomedical and Biomolecular Sciences, University of Portsmouth, Portsmouth, PO1 2DY, UK., Bufton JC; School of Biological Sciences and Institute of Biomedical and Biomolecular Sciences, University of Portsmouth, Portsmouth, PO1 2DY, UK., Lourenco DC; School of Biological Sciences and Institute of Biomedical and Biomolecular Sciences, University of Portsmouth, Portsmouth, PO1 2DY, UK., Gowers DM; School of Biological Sciences and Institute of Biomedical and Biomolecular Sciences, University of Portsmouth, Portsmouth, PO1 2DY, UK., Pickford AR; School of Biological Sciences and Institute of Biomedical and Biomolecular Sciences, University of Portsmouth, Portsmouth, PO1 2DY, UK., Cox PA; School of Pharmacy and Biomedical Sciences and Institute of Biomedical and Biomolecular Sciences, University of Portsmouth, Portsmouth, PO1 2DT, UK., Vincent HA; School of Biological Sciences and Institute of Biomedical and Biomolecular Sciences, University of Portsmouth, Portsmouth, PO1 2DY, UK., Callaghan AJ; School of Biological Sciences and Institute of Biomedical and Biomolecular Sciences, University of Portsmouth, Portsmouth, PO1 2DY, UK.
Jazyk:	angličtina
Zdroj:	Nucleic acids research [Nucleic Acids Res] 2017 May 05; Vol. 45 (8), pp. 4655-4666.
DOI:	10.1093/nar/gkx114
Abstrakt:	Ribonucleases play essential roles in all aspects of RNA metabolism, including the coordination of post-transcriptional gene regulation that allows organisms to respond to internal changes and environmental stimuli. However, as inherently destructive enzymes, their activity must be carefully controlled. Recent research exemplifies the repertoire of regulatory strategies employed by ribonucleases. The activity of the phosphorolytic exoribonuclease, polynucleotide phosphorylase (PNPase), has previously been shown to be modulated by the Krebs cycle metabolite citrate in Escherichia coli. Here, we provide evidence for the existence of citrate-mediated inhibition of ribonucleases in all three domains of life. In silico molecular docking studies predict that citrate will bind not only to bacterial PNPases from E. coli and Streptomyces antibioticus, but also PNPase from human mitochondria and the structurally and functionally related archaeal exosome complex from Sulfolobus solfataricus. Critically, we show experimentally that citrate also inhibits the exoribonuclease activity of bacterial, eukaryotic and archaeal PNPase homologues in vitro. Furthermore, bioinformatics data, showing key citrate-binding motifs conserved across a broad range of PNPase homologues, suggests that this regulatory mechanism may be widespread. Overall, our data highlight a communicative link between ribonuclease activity and central metabolism that may have been conserved through the course of evolution. (© The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.)
Databáze:	MEDLINE
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