Structure-based prediction and characterization of photo-crosslinking in native protein–RNA complexes
Abstract UV-crosslinking of protein and RNA in direct contacts has been widely used to study protein-RNA complexes while our understanding of the photo-crosslinking mechanisms remains poor. This knowledge gap is due to the challenge of precisely mapping the crosslink sites in protein and RNA simulta...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-03-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-46429-y |
| _version_ | 1797259173724946432 |
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| author | Huijuan Feng Xiang-Jun Lu Suvrajit Maji Linxi Liu Dmytro Ustianenko Noam D. Rudnick Chaolin Zhang |
| author_facet | Huijuan Feng Xiang-Jun Lu Suvrajit Maji Linxi Liu Dmytro Ustianenko Noam D. Rudnick Chaolin Zhang |
| author_sort | Huijuan Feng |
| collection | DOAJ |
| description | Abstract UV-crosslinking of protein and RNA in direct contacts has been widely used to study protein-RNA complexes while our understanding of the photo-crosslinking mechanisms remains poor. This knowledge gap is due to the challenge of precisely mapping the crosslink sites in protein and RNA simultaneously in their native sequence and structural contexts. Here we systematically analyze protein-RNA interactions and photo-crosslinking by bridging crosslinked nucleotides and amino acids mapped using different assays with protein-RNA complex structures. We developed a computational method PxR3D-map which reliably predicts crosslink sites using structural information characterizing protein-RNA interaction interfaces. Analysis of the informative features revealed that photo-crosslinking is facilitated by base stacking with not only aromatic residues, but also dipeptide bonds that involve glycine, and distinct mechanisms are utilized by different RNA-binding domains. Our work suggests protein-RNA photo-crosslinking is highly selective in the cellular environment, which can guide data interpretation and further technology development for UV-crosslinking-based assays. |
| first_indexed | 2024-04-24T23:05:13Z |
| format | Article |
| id | doaj.art-ba91412f3e74451492761b3a20f6e1bd |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-04-24T23:05:13Z |
| publishDate | 2024-03-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-ba91412f3e74451492761b3a20f6e1bd2024-03-17T12:30:59ZengNature PortfolioNature Communications2041-17232024-03-0115111410.1038/s41467-024-46429-yStructure-based prediction and characterization of photo-crosslinking in native protein–RNA complexesHuijuan Feng0Xiang-Jun Lu1Suvrajit Maji2Linxi Liu3Dmytro Ustianenko4Noam D. Rudnick5Chaolin Zhang6Department of Biostatistics and Computational Biology, School of Life Sciences, Fudan UniversityDepartment of Biological Sciences, Columbia UniversityDepartment of Systems Biology, Columbia UniversityDepartment of Statistics, Columbia UniversityDepartment of Systems Biology, Columbia UniversityDepartment of Biochemistry and Molecular Biophysics, Columbia UniversityDepartment of Systems Biology, Columbia UniversityAbstract UV-crosslinking of protein and RNA in direct contacts has been widely used to study protein-RNA complexes while our understanding of the photo-crosslinking mechanisms remains poor. This knowledge gap is due to the challenge of precisely mapping the crosslink sites in protein and RNA simultaneously in their native sequence and structural contexts. Here we systematically analyze protein-RNA interactions and photo-crosslinking by bridging crosslinked nucleotides and amino acids mapped using different assays with protein-RNA complex structures. We developed a computational method PxR3D-map which reliably predicts crosslink sites using structural information characterizing protein-RNA interaction interfaces. Analysis of the informative features revealed that photo-crosslinking is facilitated by base stacking with not only aromatic residues, but also dipeptide bonds that involve glycine, and distinct mechanisms are utilized by different RNA-binding domains. Our work suggests protein-RNA photo-crosslinking is highly selective in the cellular environment, which can guide data interpretation and further technology development for UV-crosslinking-based assays.https://doi.org/10.1038/s41467-024-46429-y |
| spellingShingle | Huijuan Feng Xiang-Jun Lu Suvrajit Maji Linxi Liu Dmytro Ustianenko Noam D. Rudnick Chaolin Zhang Structure-based prediction and characterization of photo-crosslinking in native protein–RNA complexes Nature Communications |
| title | Structure-based prediction and characterization of photo-crosslinking in native protein–RNA complexes |
| title_full | Structure-based prediction and characterization of photo-crosslinking in native protein–RNA complexes |
| title_fullStr | Structure-based prediction and characterization of photo-crosslinking in native protein–RNA complexes |
| title_full_unstemmed | Structure-based prediction and characterization of photo-crosslinking in native protein–RNA complexes |
| title_short | Structure-based prediction and characterization of photo-crosslinking in native protein–RNA complexes |
| title_sort | structure based prediction and characterization of photo crosslinking in native protein rna complexes |
| url | https://doi.org/10.1038/s41467-024-46429-y |
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