4.8 Article

Multifaceted impact of a nucleoside monophosphate kinase on 5′-end-dependent mRNA degradation in bacteria

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NUCLEIC ACIDS RESEARCH
卷 49, 期 19, 页码 11038-11049

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OXFORD UNIV PRESS
DOI: 10.1093/nar/gkab884

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  1. National Institutes of Health [F32GM101962, R01GM035769]

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A key pathway for mRNA degradation in bacterial cells involves the conversion of initial 5'-terminal triphosphate to monophosphate, rendering transcripts vulnerable to ribonucleases. Cytidylate kinase has been identified as another protein affecting mRNA degradation in E. coli by influencing the phosphorylation state of RNA and nucleotide incorporation during transcription. These findings suggest dual signaling pathways by which nucleotide metabolism can impact mRNA degradation in bacteria.
A key pathway for mRNA degradation in bacterial cells begins with conversion of the initial 5 '-terminal triphosphate to a monophosphate, a modification that renders transcripts more vulnerable to attack by ribonucleases whose affinity for monophosphorylated 5 ' ends potentiates their catalytic efficacy. In Escherichia coli, the only proteins known to be important for controlling degradation via this pathway are the RNA pyrophosphohydrolase RppH, its heteromeric partner DapF, and the 5 '-monophosphate-assisted endonucleases RNase E and RNase G. We have now identified the metabolic enzyme cytidylate kinase as another protein that affects rates of 5 '-end-dependent mRNA degradation in E. coli. It does so by utilizing two distinct mechanisms to influence the 5 '-terminal phosphorylation state of RNA, each dependent on the catalytic activity of cytidylate kinase and not its mere presence in cells. First, this enzyme acts in conjunction with DapF to stimulate the conversion of 5 ' triphosphates to monophosphates by RppH. In addition, it suppresses the direct synthesis of monophosphorylated transcripts that begin with cytidine by reducing the cellular concentration of cytidine monophosphate, thereby disfavoring the 5 '-terminal incorporation of this nucleotide by RNA polymerase during transcription initiation. Together, these findings suggest dual signaling pathways by which nucleotide metabolism can impact mRNA degradation in bacteria.

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