Glutamine synthetase mRNA releases sRNA from its 3´UTR to regulate carbon/nitrogen metabolic balance in Enterobacteriaceae
- University of Tsukuba, Japan
- Keio University, Japan
- Chiba University, Japan
- Kyushu University, Japan
- Tokyo Institute of Technology, Japan
Abstract
Glutamine synthetase (GS) is the key enzyme of nitrogen assimilation induced under nitrogen limiting conditions. The carbon skeleton of glutamate and glutamine, 2-oxoglutarate, is supplied from the TCA cycle, but how this metabolic flow is controlled in response to nitrogen availability remains unknown. We show that the expression of the E1o component of 2-oxoglutarate dehydrogenase, SucA, is repressed under nitrogen limitation in Salmonella enterica and E coli. The repression is exerted at the post-transcriptional level by an Hfq-dependent sRNA GlnZ generated from the 3´UTR of the GS-encoding glnA mRNA. Enterobacterial GlnZ variants contain a conserved seed sequence and primarily regulate sucA through base-pairing far upstream of the translation initiation region. During growth on glutamine as the nitrogen source, the glnA 3´UTR deletion mutants expressed SucA at higher levels than the S. enterica and E. coli wild-type strains, respectively. In E. coli, the transcriptional regulator Nac also participates in the repression of sucA. Lastly, this study clarifies that the release of GlnZ from the glnA mRNA by RNase E is essential for the post-transcriptional regulation of sucA. Thus the mRNA coordinates the two independent functions to balance the supply and demand of the fundamental metabolites.
Data availability
The RNA-seq data have been deposited in DDBJ DRA under accession number DRA012682.
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Regulatory network analysis of mRNA 3'UTRs in SalmonellaDDBJ Sequence Read Archive, DRA012682.
Article and author information
Author details
Masatoshi Miyakoshi
Funding
Japan Society for the Promotion of Science (JP19H03464)
- Masatoshi Miyakoshi
Japan Society for the Promotion of Science (JP19KK0406)
- Masatoshi Miyakoshi
Japan Society for the Promotion of Science (JP21K19063)
- Masatoshi Miyakoshi
Japan Society for the Promotion of Science (JP22H02236)
- Kan Tanaka
Japan Society for the Promotion of Science (JP16H06279)
- Hiroki Takahashi
- Tetsuya Hayashi
Waksman Foundation of Japan
- Masatoshi Miyakoshi
Takeda Medical Research Foundation
- Masatoshi Miyakoshi
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2022, Miyakoshi et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Glutamine synthetase mRNA releases sRNA from its 3´UTR to regulate carbon/nitrogen metabolic balance in Enterobacteriaceae
eLife 11:e82411.
https://doi.org/10.7554/eLife.82411
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