Hidden Structural Modules in a Cooperative RNA Folding Transition
Summary: Large-scale, cooperative rearrangements underlie the functions of RNA in RNA-protein machines and gene regulation. To understand how such rearrangements are orchestrated, we used high-throughput chemical footprinting to dissect a seemingly concerted rearrangement in P5abc RNA, a paradigm of...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2018-03-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124718303115 |
| _version_ | 1818849735651360768 |
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| author | Brant Gracia Hashim M. Al-Hashimi Namita Bisaria Rhiju Das Daniel Herschlag Rick Russell |
| author_facet | Brant Gracia Hashim M. Al-Hashimi Namita Bisaria Rhiju Das Daniel Herschlag Rick Russell |
| author_sort | Brant Gracia |
| collection | DOAJ |
| description | Summary: Large-scale, cooperative rearrangements underlie the functions of RNA in RNA-protein machines and gene regulation. To understand how such rearrangements are orchestrated, we used high-throughput chemical footprinting to dissect a seemingly concerted rearrangement in P5abc RNA, a paradigm of RNA folding studies. With mutations that systematically disrupt or restore putative structural elements, we found that this transition reflects local folding of structural modules, with modest and incremental cooperativity that results in concerted behavior. First, two distant secondary structure changes are coupled through a bridging three-way junction and Mg2+-dependent tertiary structure. Second, long-range contacts are formed between modules, resulting in additional cooperativity. Given the sparseness of RNA tertiary contacts after secondary structure formation, we expect that modular folding and incremental cooperativity are generally important for specifying functional structures while also providing productive kinetic paths to these structures. Additionally, we expect our approach to be useful for uncovering modularity in other complex RNAs. : Gracia et al. dissect a complex RNA folding transition with changes in secondary and tertiary structure. They show that modular structures fold and interact with limited, incremental cooperativity. This cooperativity is sufficient to give a concerted folding transition and may balance competing biological demands on RNA stability and folding efficiency. Keywords: folding cooperativity, group I intron, kinetics, RNA folding, RNA structure probing, RNA tertiary structure, tetrahymena ribozyme |
| first_indexed | 2024-12-19T06:37:58Z |
| format | Article |
| id | doaj.art-18138734a5714f62b4f12fef9807c357 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-19T06:37:58Z |
| publishDate | 2018-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-18138734a5714f62b4f12fef9807c3572022-12-21T20:32:10ZengElsevierCell Reports2211-12472018-03-01221232403250Hidden Structural Modules in a Cooperative RNA Folding TransitionBrant Gracia0Hashim M. Al-Hashimi1Namita Bisaria2Rhiju Das3Daniel Herschlag4Rick Russell5Department of Molecular Biosciences and the Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, TX 78712, USADepartment of Biochemistry, Duke University Medical Center, Durham, NC 27710, USA; Department of Chemistry, Duke University Medical Center, Durham, NC 27710, USADepartment of Biochemistry, Stanford University, Stanford, CA 94305, USADepartment of Biochemistry, Stanford University, Stanford, CA 94305, USADepartment of Biochemistry, Stanford University, Stanford, CA 94305, USADepartment of Molecular Biosciences and the Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, TX 78712, USA; Corresponding authorSummary: Large-scale, cooperative rearrangements underlie the functions of RNA in RNA-protein machines and gene regulation. To understand how such rearrangements are orchestrated, we used high-throughput chemical footprinting to dissect a seemingly concerted rearrangement in P5abc RNA, a paradigm of RNA folding studies. With mutations that systematically disrupt or restore putative structural elements, we found that this transition reflects local folding of structural modules, with modest and incremental cooperativity that results in concerted behavior. First, two distant secondary structure changes are coupled through a bridging three-way junction and Mg2+-dependent tertiary structure. Second, long-range contacts are formed between modules, resulting in additional cooperativity. Given the sparseness of RNA tertiary contacts after secondary structure formation, we expect that modular folding and incremental cooperativity are generally important for specifying functional structures while also providing productive kinetic paths to these structures. Additionally, we expect our approach to be useful for uncovering modularity in other complex RNAs. : Gracia et al. dissect a complex RNA folding transition with changes in secondary and tertiary structure. They show that modular structures fold and interact with limited, incremental cooperativity. This cooperativity is sufficient to give a concerted folding transition and may balance competing biological demands on RNA stability and folding efficiency. Keywords: folding cooperativity, group I intron, kinetics, RNA folding, RNA structure probing, RNA tertiary structure, tetrahymena ribozymehttp://www.sciencedirect.com/science/article/pii/S2211124718303115 |
| spellingShingle | Brant Gracia Hashim M. Al-Hashimi Namita Bisaria Rhiju Das Daniel Herschlag Rick Russell Hidden Structural Modules in a Cooperative RNA Folding Transition Cell Reports |
| title | Hidden Structural Modules in a Cooperative RNA Folding Transition |
| title_full | Hidden Structural Modules in a Cooperative RNA Folding Transition |
| title_fullStr | Hidden Structural Modules in a Cooperative RNA Folding Transition |
| title_full_unstemmed | Hidden Structural Modules in a Cooperative RNA Folding Transition |
| title_short | Hidden Structural Modules in a Cooperative RNA Folding Transition |
| title_sort | hidden structural modules in a cooperative rna folding transition |
| url | http://www.sciencedirect.com/science/article/pii/S2211124718303115 |
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