Recognition and cleavage mechanism of intron-containing pre-tRNA by human TSEN endonuclease complex
Abstract Removal of introns from transfer RNA precursors (pre-tRNAs) occurs in all living organisms. This is a vital phase in the maturation and functionality of tRNA. Here we present a 3.2 Å-resolution cryo-EM structure of an active human tRNA splicing endonuclease complex bound to an intron-contai...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-09-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-41845-y |
| _version_ | 1797558201207488512 |
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| author | Ling Yuan Yaoyao Han Jiazheng Zhao Yixiao Zhang Yadong Sun |
| author_facet | Ling Yuan Yaoyao Han Jiazheng Zhao Yixiao Zhang Yadong Sun |
| author_sort | Ling Yuan |
| collection | DOAJ |
| description | Abstract Removal of introns from transfer RNA precursors (pre-tRNAs) occurs in all living organisms. This is a vital phase in the maturation and functionality of tRNA. Here we present a 3.2 Å-resolution cryo-EM structure of an active human tRNA splicing endonuclease complex bound to an intron-containing pre-tRNA. TSEN54, along with the unique regions of TSEN34 and TSEN2, cooperatively recognizes the mature body of pre-tRNA and guides the anticodon-intron stem to the correct position for splicing. We capture the moment when the endonucleases are poised for cleavage, illuminating the molecular mechanism for both 3′ and 5′ cleavage reactions. Two insertion loops from TSEN54 and TSEN2 cover the 3′ and 5′ splice sites, respectively, trapping the scissile phosphate in the center of the catalytic triad of residues. Our findings reveal the molecular mechanism for eukaryotic pre-tRNA recognition and cleavage, as well as the evolutionary relationship between archaeal and eukaryotic TSENs. |
| first_indexed | 2024-03-10T17:27:01Z |
| format | Article |
| id | doaj.art-0b1635cc872040ffb3a2f83184114ea6 |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-10T17:27:01Z |
| publishDate | 2023-09-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-0b1635cc872040ffb3a2f83184114ea62023-11-20T10:07:22ZengNature PortfolioNature Communications2041-17232023-09-0114111010.1038/s41467-023-41845-yRecognition and cleavage mechanism of intron-containing pre-tRNA by human TSEN endonuclease complexLing Yuan0Yaoyao Han1Jiazheng Zhao2Yixiao Zhang3Yadong Sun4School of Life Science and Technology, ShanghaiTech UniversityInterdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of SciencesSchool of Life Science and Technology, ShanghaiTech UniversityInterdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of SciencesSchool of Life Science and Technology, ShanghaiTech UniversityAbstract Removal of introns from transfer RNA precursors (pre-tRNAs) occurs in all living organisms. This is a vital phase in the maturation and functionality of tRNA. Here we present a 3.2 Å-resolution cryo-EM structure of an active human tRNA splicing endonuclease complex bound to an intron-containing pre-tRNA. TSEN54, along with the unique regions of TSEN34 and TSEN2, cooperatively recognizes the mature body of pre-tRNA and guides the anticodon-intron stem to the correct position for splicing. We capture the moment when the endonucleases are poised for cleavage, illuminating the molecular mechanism for both 3′ and 5′ cleavage reactions. Two insertion loops from TSEN54 and TSEN2 cover the 3′ and 5′ splice sites, respectively, trapping the scissile phosphate in the center of the catalytic triad of residues. Our findings reveal the molecular mechanism for eukaryotic pre-tRNA recognition and cleavage, as well as the evolutionary relationship between archaeal and eukaryotic TSENs.https://doi.org/10.1038/s41467-023-41845-y |
| spellingShingle | Ling Yuan Yaoyao Han Jiazheng Zhao Yixiao Zhang Yadong Sun Recognition and cleavage mechanism of intron-containing pre-tRNA by human TSEN endonuclease complex Nature Communications |
| title | Recognition and cleavage mechanism of intron-containing pre-tRNA by human TSEN endonuclease complex |
| title_full | Recognition and cleavage mechanism of intron-containing pre-tRNA by human TSEN endonuclease complex |
| title_fullStr | Recognition and cleavage mechanism of intron-containing pre-tRNA by human TSEN endonuclease complex |
| title_full_unstemmed | Recognition and cleavage mechanism of intron-containing pre-tRNA by human TSEN endonuclease complex |
| title_short | Recognition and cleavage mechanism of intron-containing pre-tRNA by human TSEN endonuclease complex |
| title_sort | recognition and cleavage mechanism of intron containing pre trna by human tsen endonuclease complex |
| url | https://doi.org/10.1038/s41467-023-41845-y |
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