RNA folding kinetics control riboswitch sensitivity in vivo
Abstract Riboswitches are ligand-responsive gene-regulatory RNA elements that perform key roles in maintaining cellular homeostasis. Understanding how riboswitch sensitivity to ligand (EC50) is controlled is critical to explain how highly conserved aptamer domains are deployed in a variety of contex...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-01-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-55601-3 |
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| _version_ | 1832585552612818944 |
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| author | David Z. Bushhouse Jiayu Fu Julius B. Lucks |
| author_facet | David Z. Bushhouse Jiayu Fu Julius B. Lucks |
| author_sort | David Z. Bushhouse |
| collection | DOAJ |
| description | Abstract Riboswitches are ligand-responsive gene-regulatory RNA elements that perform key roles in maintaining cellular homeostasis. Understanding how riboswitch sensitivity to ligand (EC50) is controlled is critical to explain how highly conserved aptamer domains are deployed in a variety of contexts with different sensitivity demands. Here we uncover roles by which RNA folding dynamics control riboswitch sensitivity in cells. By investigating the Clostridium beijerinckii pfl ZTP riboswitch, we identify multiple mechanistic routes of altering expression platform sequence and structure to slow RNA folding, all of which enhance riboswitch sensitivity. Applying these methods to riboswitches with diverse aptamer architectures and regulatory mechanisms demonstrates the generality of our findings, indicating that any riboswitch that operates in a kinetic regime can be sensitized by slowing expression platform folding. Our results add to the growing suite of knowledge and approaches that can be used to rationally program cotranscriptional RNA folding for biotechnology applications, and suggest general RNA folding principles for understanding dynamic RNA systems in other areas of biology. |
| format | Article |
| id | doaj-art-25ab5006e6dc43fdbc2e526bf2c051eb |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-25ab5006e6dc43fdbc2e526bf2c051eb2025-01-26T12:40:44ZengNature PortfolioNature Communications2041-17232025-01-0116111510.1038/s41467-024-55601-3RNA folding kinetics control riboswitch sensitivity in vivoDavid Z. Bushhouse0Jiayu Fu1Julius B. Lucks2Interdisciplinary Biological Sciences Graduate Program, Northwestern UniversityInterdisciplinary Biological Sciences Graduate Program, Northwestern UniversityInterdisciplinary Biological Sciences Graduate Program, Northwestern UniversityAbstract Riboswitches are ligand-responsive gene-regulatory RNA elements that perform key roles in maintaining cellular homeostasis. Understanding how riboswitch sensitivity to ligand (EC50) is controlled is critical to explain how highly conserved aptamer domains are deployed in a variety of contexts with different sensitivity demands. Here we uncover roles by which RNA folding dynamics control riboswitch sensitivity in cells. By investigating the Clostridium beijerinckii pfl ZTP riboswitch, we identify multiple mechanistic routes of altering expression platform sequence and structure to slow RNA folding, all of which enhance riboswitch sensitivity. Applying these methods to riboswitches with diverse aptamer architectures and regulatory mechanisms demonstrates the generality of our findings, indicating that any riboswitch that operates in a kinetic regime can be sensitized by slowing expression platform folding. Our results add to the growing suite of knowledge and approaches that can be used to rationally program cotranscriptional RNA folding for biotechnology applications, and suggest general RNA folding principles for understanding dynamic RNA systems in other areas of biology.https://doi.org/10.1038/s41467-024-55601-3 |
| spellingShingle | David Z. Bushhouse Jiayu Fu Julius B. Lucks RNA folding kinetics control riboswitch sensitivity in vivo Nature Communications |
| title | RNA folding kinetics control riboswitch sensitivity in vivo |
| title_full | RNA folding kinetics control riboswitch sensitivity in vivo |
| title_fullStr | RNA folding kinetics control riboswitch sensitivity in vivo |
| title_full_unstemmed | RNA folding kinetics control riboswitch sensitivity in vivo |
| title_short | RNA folding kinetics control riboswitch sensitivity in vivo |
| title_sort | rna folding kinetics control riboswitch sensitivity in vivo |
| url | https://doi.org/10.1038/s41467-024-55601-3 |
| work_keys_str_mv | AT davidzbushhouse rnafoldingkineticscontrolriboswitchsensitivityinvivo AT jiayufu rnafoldingkineticscontrolriboswitchsensitivityinvivo AT juliusblucks rnafoldingkineticscontrolriboswitchsensitivityinvivo |