Glutamine synthetase mRNA releases sRNA from its 3′UTR to regulate carbon/nitrogen metabolic balance in Enterobacteriaceae
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 unkn...
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| Format: | Article |
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eLife Sciences Publications Ltd
2022-11-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/82411 |
| _version_ | 1811185146285522944 |
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| author | Masatoshi Miyakoshi Teppei Morita Asaki Kobayashi Anna Berger Hiroki Takahashi Yasuhiro Gotoh Tetsuya Hayashi Kan Tanaka |
| author_facet | Masatoshi Miyakoshi Teppei Morita Asaki Kobayashi Anna Berger Hiroki Takahashi Yasuhiro Gotoh Tetsuya Hayashi Kan Tanaka |
| author_sort | Masatoshi Miyakoshi |
| collection | DOAJ |
| description | 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 Escherichia 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. |
| first_indexed | 2024-04-11T13:24:29Z |
| format | Article |
| id | doaj.art-3d0bd954fac54bb3b7b41df4acd00bb6 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-11T13:24:29Z |
| publishDate | 2022-11-01 |
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| spelling | doaj.art-3d0bd954fac54bb3b7b41df4acd00bb62022-12-22T04:22:06ZengeLife Sciences Publications LtdeLife2050-084X2022-11-011110.7554/eLife.82411Glutamine synthetase mRNA releases sRNA from its 3′UTR to regulate carbon/nitrogen metabolic balance in EnterobacteriaceaeMasatoshi Miyakoshi0https://orcid.org/0000-0002-4901-2809Teppei Morita1https://orcid.org/0000-0001-5057-5687Asaki Kobayashi2Anna Berger3Hiroki Takahashi4https://orcid.org/0000-0001-5627-1035Yasuhiro Gotoh5Tetsuya Hayashi6https://orcid.org/0000-0001-6366-7177Kan Tanaka7https://orcid.org/0000-0001-7560-7884Department of Infection Biology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan; Transborder Medical Research Center, University of Tsukuba, Tsukuba, Japan; International Joint Degree Master’s Program in Agro-Biomedical Science in Food and Health (GIP-TRIAD), University of Tsukuba, Tsukuba, JapanInstitute for Advanced Biosciences, Keio University, Tsuruoka, Japan; Graduate School of Media and Governance, Keio University, Fujisawa, JapanTransborder Medical Research Center, University of Tsukuba, Tsukuba, JapanInternational Joint Degree Master’s Program in Agro-Biomedical Science in Food and Health (GIP-TRIAD), University of Tsukuba, Tsukuba, JapanMedical Mycology Research Center, Chiba University, Chiba, JapanDepartment of Bacteriology, Faculty of Medical Sciences, Kyushu University, Fukuoka, JapanDepartment of Bacteriology, Faculty of Medical Sciences, Kyushu University, Fukuoka, JapanLaboratory for Chemistry and Life Science, Institute of Innovative Research, Tokyo Institute of Technology, Yokohama, JapanGlutamine 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 Escherichia 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.https://elifesciences.org/articles/82411nitrogen assimilationTCA cyclesmall RNA3′UTRRNase E |
| spellingShingle | Masatoshi Miyakoshi Teppei Morita Asaki Kobayashi Anna Berger Hiroki Takahashi Yasuhiro Gotoh Tetsuya Hayashi Kan Tanaka Glutamine synthetase mRNA releases sRNA from its 3′UTR to regulate carbon/nitrogen metabolic balance in Enterobacteriaceae eLife nitrogen assimilation TCA cycle small RNA 3′UTR RNase E |
| title | Glutamine synthetase mRNA releases sRNA from its 3′UTR to regulate carbon/nitrogen metabolic balance in Enterobacteriaceae |
| title_full | Glutamine synthetase mRNA releases sRNA from its 3′UTR to regulate carbon/nitrogen metabolic balance in Enterobacteriaceae |
| title_fullStr | Glutamine synthetase mRNA releases sRNA from its 3′UTR to regulate carbon/nitrogen metabolic balance in Enterobacteriaceae |
| title_full_unstemmed | Glutamine synthetase mRNA releases sRNA from its 3′UTR to regulate carbon/nitrogen metabolic balance in Enterobacteriaceae |
| title_short | Glutamine synthetase mRNA releases sRNA from its 3′UTR to regulate carbon/nitrogen metabolic balance in Enterobacteriaceae |
| title_sort | glutamine synthetase mrna releases srna from its 3 utr to regulate carbon nitrogen metabolic balance in enterobacteriaceae |
| topic | nitrogen assimilation TCA cycle small RNA 3′UTR RNase E |
| url | https://elifesciences.org/articles/82411 |
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