Polynucleotide phosphorylase activity may be modulated by metabolites in escherichia coli
Author(s)
Type
Journal Article
Abstract
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 citrate affects the activity of Escherichia coli polynucleotide phosphorylase (PNPase) and, conversely, that cellular metabolism is affected widely by PNPase activity. An E. coli strain that requires PNPase for viability has suppressed growth in the presence of increased citrate concentration. Transcriptome analysis reveals a PNPase-mediated response to citrate, and PNPase deletion broadly impacts on the metabolome. In vitro, citrate directly binds and modulates PNPase activity, as predicted by crystallographic data. Binding of metal-chelated citrate in the active site at physiological concentrations appears to inhibit enzyme activity. However, metal-free citrate 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 citrate. 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.
Date Issued
2011-04-22
Date Acceptance
2011-02-01
Citation
Journal of Biological Chemistry, 2011, 286 (16), pp.14315-14323
ISSN
0021-9258
Publisher
American Society for Biochemistry and Molecular Biology
Start Page
14315
End Page
14323
Journal / Book Title
Journal of Biological Chemistry
Volume
286
Issue
16
Copyright Statement
© 2011 by The American Society for Biochemistry and Molecular Biology, Inc.
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Author's Choice—Final version full access.
Creative Commons Attribution Non-Commercial License applies to Author Choice Articles http://creativecommons.org/licenses/by-nc/3.0/.
License URL
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000289556200054&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Subjects
Science & Technology
Life Sciences & Biomedicine
Biochemistry & Molecular Biology
RNA DEGRADOSOME
MESSENGER-RNA
SALMONELLA-ENTERICA
GLYCOLYTIC-ENZYMES
RIBONUCLEASE-II
DECAY
VIRULENCE
RECONSTITUTION
MITOCHONDRIA
DEGRADATION
Publication Status
Published
Date Publish Online
2011-02-14