Identification of HDV-like theta ribozymes involved in tRNA-based recoding of gut bacteriophages
Abstract Trillions of microorganisms, collectively known as the microbiome, inhabit our bodies with the gut microbiome being of particular interest in biomedical research. Bacteriophages, the dominant virome constituents, can utilize suppressor tRNAs to switch to alternative genetic codes (e.g., the...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-02-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-45653-w |
| _version_ | 1797274017324859392 |
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| author | Kasimir Kienbeck Lukas Malfertheiner Susann Zelger-Paulus Silke Johannsen Christian von Mering Roland K. O. Sigel |
| author_facet | Kasimir Kienbeck Lukas Malfertheiner Susann Zelger-Paulus Silke Johannsen Christian von Mering Roland K. O. Sigel |
| author_sort | Kasimir Kienbeck |
| collection | DOAJ |
| description | Abstract Trillions of microorganisms, collectively known as the microbiome, inhabit our bodies with the gut microbiome being of particular interest in biomedical research. Bacteriophages, the dominant virome constituents, can utilize suppressor tRNAs to switch to alternative genetic codes (e.g., the UAG stop-codon is reassigned to glutamine) while infecting hosts with the standard bacterial code. However, what triggers this switch and how the bacteriophage manipulates its host is poorly understood. Here, we report the discovery of a subgroup of minimal hepatitis delta virus (HDV)-like ribozymes – theta ribozymes – potentially involved in the code switch leading to the expression of recoded lysis and structural phage genes. We demonstrate their HDV-like self-scission behavior in vitro and find them in an unreported context often located with their cleavage site adjacent to tRNAs, indicating a role in viral tRNA maturation and/or regulation. Every fifth associated tRNA is a suppressor tRNA, further strengthening our hypothesis. The vast abundance of tRNA-associated theta ribozymes – we provide 1753 unique examples – highlights the importance of small ribozymes as an alternative to large enzymes that usually process tRNA 3’-ends. Our discovery expands the short list of biological functions of small HDV-like ribozymes and introduces a previously unknown player likely involved in the code switch of certain recoded gut bacteriophages. |
| first_indexed | 2024-03-07T14:52:23Z |
| format | Article |
| id | doaj.art-3b18586ea9f147b78ee30086813aa9bb |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-07T14:52:23Z |
| publishDate | 2024-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-3b18586ea9f147b78ee30086813aa9bb2024-03-05T19:36:53ZengNature PortfolioNature Communications2041-17232024-02-0115111010.1038/s41467-024-45653-wIdentification of HDV-like theta ribozymes involved in tRNA-based recoding of gut bacteriophagesKasimir Kienbeck0Lukas Malfertheiner1Susann Zelger-Paulus2Silke Johannsen3Christian von Mering4Roland K. O. Sigel5Department of Chemistry, University of ZurichDepartment of Molecular Life Sciences and Swiss Institute of Bioinformatics, University of ZurichDepartment of Chemistry, University of ZurichDepartment of Chemistry, University of ZurichDepartment of Molecular Life Sciences and Swiss Institute of Bioinformatics, University of ZurichDepartment of Chemistry, University of ZurichAbstract Trillions of microorganisms, collectively known as the microbiome, inhabit our bodies with the gut microbiome being of particular interest in biomedical research. Bacteriophages, the dominant virome constituents, can utilize suppressor tRNAs to switch to alternative genetic codes (e.g., the UAG stop-codon is reassigned to glutamine) while infecting hosts with the standard bacterial code. However, what triggers this switch and how the bacteriophage manipulates its host is poorly understood. Here, we report the discovery of a subgroup of minimal hepatitis delta virus (HDV)-like ribozymes – theta ribozymes – potentially involved in the code switch leading to the expression of recoded lysis and structural phage genes. We demonstrate their HDV-like self-scission behavior in vitro and find them in an unreported context often located with their cleavage site adjacent to tRNAs, indicating a role in viral tRNA maturation and/or regulation. Every fifth associated tRNA is a suppressor tRNA, further strengthening our hypothesis. The vast abundance of tRNA-associated theta ribozymes – we provide 1753 unique examples – highlights the importance of small ribozymes as an alternative to large enzymes that usually process tRNA 3’-ends. Our discovery expands the short list of biological functions of small HDV-like ribozymes and introduces a previously unknown player likely involved in the code switch of certain recoded gut bacteriophages.https://doi.org/10.1038/s41467-024-45653-w |
| spellingShingle | Kasimir Kienbeck Lukas Malfertheiner Susann Zelger-Paulus Silke Johannsen Christian von Mering Roland K. O. Sigel Identification of HDV-like theta ribozymes involved in tRNA-based recoding of gut bacteriophages Nature Communications |
| title | Identification of HDV-like theta ribozymes involved in tRNA-based recoding of gut bacteriophages |
| title_full | Identification of HDV-like theta ribozymes involved in tRNA-based recoding of gut bacteriophages |
| title_fullStr | Identification of HDV-like theta ribozymes involved in tRNA-based recoding of gut bacteriophages |
| title_full_unstemmed | Identification of HDV-like theta ribozymes involved in tRNA-based recoding of gut bacteriophages |
| title_short | Identification of HDV-like theta ribozymes involved in tRNA-based recoding of gut bacteriophages |
| title_sort | identification of hdv like theta ribozymes involved in trna based recoding of gut bacteriophages |
| url | https://doi.org/10.1038/s41467-024-45653-w |
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