Girolline is a sequence context-selective modulator of eIF5A activity
Abstract Natural products have a long history of providing probes into protein biosynthesis, with many of these compounds serving as therapeutics. The marine natural product girolline has been described as an inhibitor of protein synthesis. Its precise mechanism of action, however, has remained unkn...
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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/s41467-024-54838-2 |
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| author | Tilman Schneider-Poetsch Yongjun Dang Wakana Iwasaki Mayumi Arata Yuichi Shichino Ali Al Mourabit Celine Moriou Daniel Romo Jun O. Liu Takuhiro Ito Shintaro Iwasaki Minoru Yoshida |
| author_facet | Tilman Schneider-Poetsch Yongjun Dang Wakana Iwasaki Mayumi Arata Yuichi Shichino Ali Al Mourabit Celine Moriou Daniel Romo Jun O. Liu Takuhiro Ito Shintaro Iwasaki Minoru Yoshida |
| author_sort | Tilman Schneider-Poetsch |
| collection | DOAJ |
| description | Abstract Natural products have a long history of providing probes into protein biosynthesis, with many of these compounds serving as therapeutics. The marine natural product girolline has been described as an inhibitor of protein synthesis. Its precise mechanism of action, however, has remained unknown. The data we present here suggests that girolline is a sequence-selective modulator of translation factor eIF5A. Girolline interferes with ribosome-eIF5A interaction and induces ribosome stalling where translational progress is impeded, including on AAA-encoded lysine. Our data furthermore indicate that eIF5A plays a physiological role in ribosome-associated quality control and in maintaining the efficiency of translational progress. Girolline helped to deepen our understanding of the interplay between protein production and quality control in a physiological setting and offers a potent chemical tool to selectively modulate gene expression. |
| format | Article |
| id | doaj-art-80cf9918d5894e5abe467b1dcbb4d43a |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-80cf9918d5894e5abe467b1dcbb4d43a2025-01-12T12:30:59ZengNature PortfolioNature Communications2041-17232025-01-0116111310.1038/s41467-024-54838-2Girolline is a sequence context-selective modulator of eIF5A activityTilman Schneider-Poetsch0Yongjun Dang1Wakana Iwasaki2Mayumi Arata3Yuichi Shichino4Ali Al Mourabit5Celine Moriou6Daniel Romo7Jun O. Liu8Takuhiro Ito9Shintaro Iwasaki10Minoru Yoshida11Chemical Genomics Research Group, RIKEN Center for Sustainable Resource Science, WakoBasic Medicine Research and Innovation Center for Novel Target and Therapeutic Intervention, Ministry of Education, The Second Affiliated Hospital of Chongqing Medical University, College of Pharmacy, Chongqing Medical UniversityLaboratory for Translation Structural Biology, RIKEN Center for Biosystems Dynamics ResearchDrug Discovery Seed Compounds Exploratory Unit, RIKEN Center for Sustainable Resource Science, WakoRNA Systems Biochemistry Laboratory, RIKEN Cluster for Pioneering Research, WakoInstitut de Chimie des Substances Naturelles, CNRS UPR 2301, Univ. Paris-Sud, Université Paris-SaclayInstitut de Chimie des Substances Naturelles, CNRS UPR 2301, Univ. Paris-Sud, Université Paris-SaclayDepartment of Chemistry and Biochemistry, Baylor University, One Bear PlaceDepartment of Pharmacology and Molecular Sciences, The Johns Hopkins University School of MedicineLaboratory for Translation Structural Biology, RIKEN Center for Biosystems Dynamics ResearchRNA Systems Biochemistry Laboratory, RIKEN Cluster for Pioneering Research, WakoChemical Genomics Research Group, RIKEN Center for Sustainable Resource Science, WakoAbstract Natural products have a long history of providing probes into protein biosynthesis, with many of these compounds serving as therapeutics. The marine natural product girolline has been described as an inhibitor of protein synthesis. Its precise mechanism of action, however, has remained unknown. The data we present here suggests that girolline is a sequence-selective modulator of translation factor eIF5A. Girolline interferes with ribosome-eIF5A interaction and induces ribosome stalling where translational progress is impeded, including on AAA-encoded lysine. Our data furthermore indicate that eIF5A plays a physiological role in ribosome-associated quality control and in maintaining the efficiency of translational progress. Girolline helped to deepen our understanding of the interplay between protein production and quality control in a physiological setting and offers a potent chemical tool to selectively modulate gene expression.https://doi.org/10.1038/s41467-024-54838-2 |
| spellingShingle | Tilman Schneider-Poetsch Yongjun Dang Wakana Iwasaki Mayumi Arata Yuichi Shichino Ali Al Mourabit Celine Moriou Daniel Romo Jun O. Liu Takuhiro Ito Shintaro Iwasaki Minoru Yoshida Girolline is a sequence context-selective modulator of eIF5A activity Nature Communications |
| title | Girolline is a sequence context-selective modulator of eIF5A activity |
| title_full | Girolline is a sequence context-selective modulator of eIF5A activity |
| title_fullStr | Girolline is a sequence context-selective modulator of eIF5A activity |
| title_full_unstemmed | Girolline is a sequence context-selective modulator of eIF5A activity |
| title_short | Girolline is a sequence context-selective modulator of eIF5A activity |
| title_sort | girolline is a sequence context selective modulator of eif5a activity |
| url | https://doi.org/10.1038/s41467-024-54838-2 |
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