Cobalamin Riboswitches Are Broadly Sensitive to Corrinoid Cofactors to Enable an Efficient Gene Regulatory Strategy
ABSTRACT In bacteria, many essential metabolic processes are controlled by riboswitches, gene regulatory RNAs that directly bind and detect metabolites. Highly specific effector binding enables riboswitches to respond to a single biologically relevant metabolite. Cobalamin riboswitches are a potenti...
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| Format: | Article |
| Language: | English |
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American Society for Microbiology
2022-10-01
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| Series: | mBio |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/mbio.01121-22 |
| _version_ | 1797989765588451328 |
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| author | Kristopher J. Kennedy Florian J. Widner Olga M. Sokolovskaya Lina V. Innocent Rebecca R. Procknow Kenny C. Mok Michiko E. Taga |
| author_facet | Kristopher J. Kennedy Florian J. Widner Olga M. Sokolovskaya Lina V. Innocent Rebecca R. Procknow Kenny C. Mok Michiko E. Taga |
| author_sort | Kristopher J. Kennedy |
| collection | DOAJ |
| description | ABSTRACT In bacteria, many essential metabolic processes are controlled by riboswitches, gene regulatory RNAs that directly bind and detect metabolites. Highly specific effector binding enables riboswitches to respond to a single biologically relevant metabolite. Cobalamin riboswitches are a potential exception because over a dozen chemically similar but functionally distinct cobalamin variants (corrinoid cofactors) exist in nature. Here, we measured cobalamin riboswitch activity in vivo using a Bacillus subtilis fluorescent reporter system and found, among 38 tested riboswitches, a subset responded to corrinoids promiscuously, while others were semiselective. Analyses of chimeric riboswitches and structural models indicate, unlike other riboswitch classes, cobalamin riboswitches indirectly differentiate among corrinoids by sensing differences in their structural conformation. This regulatory strategy aligns riboswitch-corrinoid specificity with cellular corrinoid requirements in a B. subtilis model. Thus, bacteria can employ broadly sensitive riboswitches to cope with the chemical diversity of essential metabolites. IMPORTANCE Some bacterial mRNAs contain a region called a riboswitch which controls gene expression by binding to a metabolite in the cell. Typically, riboswitches sense and respond to a limited range of cellular metabolites, often just one type. In this work, we found the cobalamin (vitamin B12) riboswitch class is an exception, capable of sensing and responding to multiple variants of B12—collectively called corrinoids. We found cobalamin riboswitches vary in corrinoid specificity with some riboswitches responding to each of the corrinoids we tested, while others responding only to a subset of corrinoids. Our results suggest the latter class of riboswitches sense intrinsic conformational differences among corrinoids in order to support the corrinoid-specific needs of the cell. These findings provide insight into how bacteria sense and respond to an exceptionally diverse, often essential set of enzyme cofactors. |
| first_indexed | 2024-04-11T08:25:35Z |
| format | Article |
| id | doaj.art-5943f31f144842118608dbc97dcae233 |
| institution | Directory Open Access Journal |
| issn | 2150-7511 |
| language | English |
| last_indexed | 2024-04-11T08:25:35Z |
| publishDate | 2022-10-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | mBio |
| spelling | doaj.art-5943f31f144842118608dbc97dcae2332022-12-22T04:34:47ZengAmerican Society for MicrobiologymBio2150-75112022-10-0113510.1128/mbio.01121-22Cobalamin Riboswitches Are Broadly Sensitive to Corrinoid Cofactors to Enable an Efficient Gene Regulatory StrategyKristopher J. Kennedy0Florian J. Widner1Olga M. Sokolovskaya2Lina V. Innocent3Rebecca R. Procknow4Kenny C. Mok5Michiko E. Taga6Department of Plant and Microbial Biology, University of California, Berkeley, Berkeley, California, USADepartment of Plant and Microbial Biology, University of California, Berkeley, Berkeley, California, USADepartment of Plant and Microbial Biology, University of California, Berkeley, Berkeley, California, USADepartment of Plant and Microbial Biology, University of California, Berkeley, Berkeley, California, USADepartment of Plant and Microbial Biology, University of California, Berkeley, Berkeley, California, USADepartment of Plant and Microbial Biology, University of California, Berkeley, Berkeley, California, USADepartment of Plant and Microbial Biology, University of California, Berkeley, Berkeley, California, USAABSTRACT In bacteria, many essential metabolic processes are controlled by riboswitches, gene regulatory RNAs that directly bind and detect metabolites. Highly specific effector binding enables riboswitches to respond to a single biologically relevant metabolite. Cobalamin riboswitches are a potential exception because over a dozen chemically similar but functionally distinct cobalamin variants (corrinoid cofactors) exist in nature. Here, we measured cobalamin riboswitch activity in vivo using a Bacillus subtilis fluorescent reporter system and found, among 38 tested riboswitches, a subset responded to corrinoids promiscuously, while others were semiselective. Analyses of chimeric riboswitches and structural models indicate, unlike other riboswitch classes, cobalamin riboswitches indirectly differentiate among corrinoids by sensing differences in their structural conformation. This regulatory strategy aligns riboswitch-corrinoid specificity with cellular corrinoid requirements in a B. subtilis model. Thus, bacteria can employ broadly sensitive riboswitches to cope with the chemical diversity of essential metabolites. IMPORTANCE Some bacterial mRNAs contain a region called a riboswitch which controls gene expression by binding to a metabolite in the cell. Typically, riboswitches sense and respond to a limited range of cellular metabolites, often just one type. In this work, we found the cobalamin (vitamin B12) riboswitch class is an exception, capable of sensing and responding to multiple variants of B12—collectively called corrinoids. We found cobalamin riboswitches vary in corrinoid specificity with some riboswitches responding to each of the corrinoids we tested, while others responding only to a subset of corrinoids. Our results suggest the latter class of riboswitches sense intrinsic conformational differences among corrinoids in order to support the corrinoid-specific needs of the cell. These findings provide insight into how bacteria sense and respond to an exceptionally diverse, often essential set of enzyme cofactors.https://journals.asm.org/doi/10.1128/mbio.01121-22Bacillus subtilisRNA biologycobalamincoenzymecofactorcorrinoid |
| spellingShingle | Kristopher J. Kennedy Florian J. Widner Olga M. Sokolovskaya Lina V. Innocent Rebecca R. Procknow Kenny C. Mok Michiko E. Taga Cobalamin Riboswitches Are Broadly Sensitive to Corrinoid Cofactors to Enable an Efficient Gene Regulatory Strategy mBio Bacillus subtilis RNA biology cobalamin coenzyme cofactor corrinoid |
| title | Cobalamin Riboswitches Are Broadly Sensitive to Corrinoid Cofactors to Enable an Efficient Gene Regulatory Strategy |
| title_full | Cobalamin Riboswitches Are Broadly Sensitive to Corrinoid Cofactors to Enable an Efficient Gene Regulatory Strategy |
| title_fullStr | Cobalamin Riboswitches Are Broadly Sensitive to Corrinoid Cofactors to Enable an Efficient Gene Regulatory Strategy |
| title_full_unstemmed | Cobalamin Riboswitches Are Broadly Sensitive to Corrinoid Cofactors to Enable an Efficient Gene Regulatory Strategy |
| title_short | Cobalamin Riboswitches Are Broadly Sensitive to Corrinoid Cofactors to Enable an Efficient Gene Regulatory Strategy |
| title_sort | cobalamin riboswitches are broadly sensitive to corrinoid cofactors to enable an efficient gene regulatory strategy |
| topic | Bacillus subtilis RNA biology cobalamin coenzyme cofactor corrinoid |
| url | https://journals.asm.org/doi/10.1128/mbio.01121-22 |
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