The SMN complex drives structural changes in human snRNAs to enable snRNP assembly
Abstract Spliceosomal snRNPs are multicomponent particles that undergo a complex maturation pathway. Human Sm-class snRNAs are generated as 3′-end extended precursors, which are exported to the cytoplasm and assembled together with Sm proteins into core RNPs by the SMN complex. Here, we provide evid...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2023-10-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-42324-0 |
| _version_ | 1797558539908022272 |
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| author | Josef Pánek Adriana Roithová Nenad Radivojević Michal Sýkora Archana Bairavasundaram Prusty Nicholas Huston Han Wan Anna Marie Pyle Utz Fischer David Staněk |
| author_facet | Josef Pánek Adriana Roithová Nenad Radivojević Michal Sýkora Archana Bairavasundaram Prusty Nicholas Huston Han Wan Anna Marie Pyle Utz Fischer David Staněk |
| author_sort | Josef Pánek |
| collection | DOAJ |
| description | Abstract Spliceosomal snRNPs are multicomponent particles that undergo a complex maturation pathway. Human Sm-class snRNAs are generated as 3′-end extended precursors, which are exported to the cytoplasm and assembled together with Sm proteins into core RNPs by the SMN complex. Here, we provide evidence that these pre-snRNA substrates contain compact, evolutionarily conserved secondary structures that overlap with the Sm binding site. These structural motifs in pre-snRNAs are predicted to interfere with Sm core assembly. We model structural rearrangements that lead to an open pre-snRNA conformation compatible with Sm protein interaction. The predicted rearrangement pathway is conserved in Metazoa and requires an external factor that initiates snRNA remodeling. We show that the essential helicase Gemin3, which is a component of the SMN complex, is crucial for snRNA structural rearrangements during snRNP maturation. The SMN complex thus facilitates ATP-driven structural changes in snRNAs that expose the Sm site and enable Sm protein binding. |
| first_indexed | 2024-03-10T17:31:54Z |
| format | Article |
| id | doaj.art-b0a36e6461ad4fc185cfe84b162ad07f |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-10T17:31:54Z |
| publishDate | 2023-10-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-b0a36e6461ad4fc185cfe84b162ad07f2023-11-20T09:59:22ZengNature PortfolioNature Communications2041-17232023-10-0114111810.1038/s41467-023-42324-0The SMN complex drives structural changes in human snRNAs to enable snRNP assemblyJosef Pánek0Adriana Roithová1Nenad Radivojević2Michal Sýkora3Archana Bairavasundaram Prusty4Nicholas Huston5Han Wan6Anna Marie Pyle7Utz Fischer8David Staněk9Laboratory of Bioinformatics, Institute of Microbiology, Czech Academy of SciencesLaboratory of RNA Biology, Institute of Molecular Genetics, Czech Academy of SciencesLaboratory of RNA Biology, Institute of Molecular Genetics, Czech Academy of SciencesLaboratory of RNA Biology, Institute of Molecular Genetics, Czech Academy of SciencesDepartment of Biochemistry, Theodor Boveri Institute, University of WürzburgDepartment of Molecular Biophysics & Biochemistry, Yale UniversityDepartment of Molecular, Cellular, and Developmental Biology, Yale UniversityDepartment of Molecular, Cellular, and Developmental Biology, Yale UniversityDepartment of Biochemistry, Theodor Boveri Institute, University of WürzburgLaboratory of RNA Biology, Institute of Molecular Genetics, Czech Academy of SciencesAbstract Spliceosomal snRNPs are multicomponent particles that undergo a complex maturation pathway. Human Sm-class snRNAs are generated as 3′-end extended precursors, which are exported to the cytoplasm and assembled together with Sm proteins into core RNPs by the SMN complex. Here, we provide evidence that these pre-snRNA substrates contain compact, evolutionarily conserved secondary structures that overlap with the Sm binding site. These structural motifs in pre-snRNAs are predicted to interfere with Sm core assembly. We model structural rearrangements that lead to an open pre-snRNA conformation compatible with Sm protein interaction. The predicted rearrangement pathway is conserved in Metazoa and requires an external factor that initiates snRNA remodeling. We show that the essential helicase Gemin3, which is a component of the SMN complex, is crucial for snRNA structural rearrangements during snRNP maturation. The SMN complex thus facilitates ATP-driven structural changes in snRNAs that expose the Sm site and enable Sm protein binding.https://doi.org/10.1038/s41467-023-42324-0 |
| spellingShingle | Josef Pánek Adriana Roithová Nenad Radivojević Michal Sýkora Archana Bairavasundaram Prusty Nicholas Huston Han Wan Anna Marie Pyle Utz Fischer David Staněk The SMN complex drives structural changes in human snRNAs to enable snRNP assembly Nature Communications |
| title | The SMN complex drives structural changes in human snRNAs to enable snRNP assembly |
| title_full | The SMN complex drives structural changes in human snRNAs to enable snRNP assembly |
| title_fullStr | The SMN complex drives structural changes in human snRNAs to enable snRNP assembly |
| title_full_unstemmed | The SMN complex drives structural changes in human snRNAs to enable snRNP assembly |
| title_short | The SMN complex drives structural changes in human snRNAs to enable snRNP assembly |
| title_sort | smn complex drives structural changes in human snrnas to enable snrnp assembly |
| url | https://doi.org/10.1038/s41467-023-42324-0 |
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