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| Formato: | Artículo científico |
| Lenguaje: | en |
| Publicado: |
Nature communications
2025
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| Materias: | |
| Acceso en línea: | https://pubmed.ncbi.nlm.nih.gov/39794322/ |
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| author | Schneider-Poetsch, Tilman Dang, Yongjun Iwasaki, Wakana Arata, Mayumi Shichino, Yuichi Al Mourabit, Ali Moriou, Celine Romo, Daniel Liu, Jun O Ito, Takuhiro Iwasaki, Shintaro Yoshida, Minoru |
| author_facet | Schneider-Poetsch, Tilman Dang, Yongjun Iwasaki, Wakana Arata, Mayumi Shichino, Yuichi Al Mourabit, Ali Moriou, Celine Romo, Daniel Liu, Jun O Ito, Takuhiro Iwasaki, Shintaro Yoshida, Minoru Schneider-Poetsch, Tilman Dang, Yongjun Iwasaki, Wakana Arata, Mayumi Shichino, Yuichi Al Mourabit, Ali Moriou, Celine Romo, Daniel Liu, Jun O Ito, Takuhiro Iwasaki, Shintaro Yoshida, Minoru |
| collection | PubMed - marine biology |
| contents | Girolline is a sequence context-selective modulator of eIF5A activity. Schneider-Poetsch, Tilman Dang, Yongjun Iwasaki, Wakana Arata, Mayumi Shichino, Yuichi Al Mourabit, Ali Moriou, Celine Romo, Daniel Liu, Jun O Ito, Takuhiro Iwasaki, Shintaro Yoshida, Minoru Eukaryotic Translation Initiation Factor 5A Peptide Initiation Factors RNA-Binding Proteins Ribosomes Humans Protein Biosynthesis Phenanthridines HEK293 Cells Lysine Guanine 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 | Artículo científico |
| id | pubmed_39794322 |
| institution | PubMed |
| language | en |
| publishDate | 2025 |
| publisher | Nature communications |
| record_format | pubmed |
| spellingShingle | Girolline is a sequence context-selective modulator of eIF5A activity. Schneider-Poetsch, Tilman Dang, Yongjun Iwasaki, Wakana Arata, Mayumi Shichino, Yuichi Al Mourabit, Ali Moriou, Celine Romo, Daniel Liu, Jun O Ito, Takuhiro Iwasaki, Shintaro Yoshida, Minoru Eukaryotic Translation Initiation Factor 5A Peptide Initiation Factors RNA-Binding Proteins Ribosomes Humans Protein Biosynthesis Phenanthridines HEK293 Cells Lysine Guanine Girolline is a sequence context-selective modulator of eIF5A activity. Schneider-Poetsch, Tilman Dang, Yongjun Iwasaki, Wakana Arata, Mayumi Shichino, Yuichi Al Mourabit, Ali Moriou, Celine Romo, Daniel Liu, Jun O Ito, Takuhiro Iwasaki, Shintaro Yoshida, Minoru Eukaryotic Translation Initiation Factor 5A Peptide Initiation Factors RNA-Binding Proteins Ribosomes Humans Protein Biosynthesis Phenanthridines HEK293 Cells Lysine Guanine 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. |
| title | Girolline is a sequence context-selective modulator of eIF5A activity. |
| topic | Eukaryotic Translation Initiation Factor 5A Peptide Initiation Factors RNA-Binding Proteins Ribosomes Humans Protein Biosynthesis Phenanthridines HEK293 Cells Lysine Guanine |
| url | https://pubmed.ncbi.nlm.nih.gov/39794322/ |