Many Activities, One Structure: Functional Plasticity of Ribozyme Folds
Catalytic RNAs, or ribozymes, are involved in a number of essential biological processes, such as replication of RNA genomes and mobile genetic elements, RNA splicing, translation, and RNA degradation. The function of ribozymes requires the formation of active sites decorated with RNA functional gro...
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| Format: | Article |
| Language: | English |
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MDPI AG
2016-11-01
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| Series: | Molecules |
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| Online Access: | http://www.mdpi.com/1420-3049/21/11/1570 |
| _version_ | 1828385107995525120 |
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| author | Matthew W.L. Lau Adrian R. Ferré-D’Amaré |
| author_facet | Matthew W.L. Lau Adrian R. Ferré-D’Amaré |
| author_sort | Matthew W.L. Lau |
| collection | DOAJ |
| description | Catalytic RNAs, or ribozymes, are involved in a number of essential biological processes, such as replication of RNA genomes and mobile genetic elements, RNA splicing, translation, and RNA degradation. The function of ribozymes requires the formation of active sites decorated with RNA functional groups within defined three-dimensional (3D) structures. The genotype (sequence) of RNAs ultimately determines what 3D structures they adopt (as a function of their environmental conditions). These 3D structures, in turn, give rise to biochemical activity, which can further elaborate them by catalytic rearrangements or association with other molecules. The fitness landscape of a non-periodic linear polymer, such as RNA, relates its primary structure to a phenotype. Two major challenges in the analysis of ribozymes is to map all possible genotypes to their corresponding catalytic activity (that is, to determine their fitness landscape experimentally), and to understand whether their genotypes and three-dimensional structures can support multiple different catalytic functions. Recently, the combined results of experiments that employ in vitro evolution methods, high-throughput sequencing and crystallographic structure determination have hinted at answers to these two questions: while the fitness landscape of ribozymes is rugged, meaning that their catalytic activity cannot be optimized by a smooth trajectory in sequence space, once an RNA achieves a stable three-dimensional fold, it can be endowed with distinctly different biochemical activities through small changes in genotype. This functional plasticity of highly structured RNAs may be particularly advantageous for the adaptation of organisms to drastic changes in selective pressure, or for the development of new biotechnological tools. |
| first_indexed | 2024-12-10T05:13:53Z |
| format | Article |
| id | doaj.art-f4d686796c65468ab965ead52182a440 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-12-10T05:13:53Z |
| publishDate | 2016-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-f4d686796c65468ab965ead52182a4402022-12-22T02:01:01ZengMDPI AGMolecules1420-30492016-11-012111157010.3390/molecules21111570molecules21111570Many Activities, One Structure: Functional Plasticity of Ribozyme FoldsMatthew W.L. Lau0Adrian R. Ferré-D’Amaré1National Heart, Lung and Blood Institute, 50 South Drive, MSC 8012, Bethesda, MD 20892-8012, USANational Heart, Lung and Blood Institute, 50 South Drive, MSC 8012, Bethesda, MD 20892-8012, USACatalytic RNAs, or ribozymes, are involved in a number of essential biological processes, such as replication of RNA genomes and mobile genetic elements, RNA splicing, translation, and RNA degradation. The function of ribozymes requires the formation of active sites decorated with RNA functional groups within defined three-dimensional (3D) structures. The genotype (sequence) of RNAs ultimately determines what 3D structures they adopt (as a function of their environmental conditions). These 3D structures, in turn, give rise to biochemical activity, which can further elaborate them by catalytic rearrangements or association with other molecules. The fitness landscape of a non-periodic linear polymer, such as RNA, relates its primary structure to a phenotype. Two major challenges in the analysis of ribozymes is to map all possible genotypes to their corresponding catalytic activity (that is, to determine their fitness landscape experimentally), and to understand whether their genotypes and three-dimensional structures can support multiple different catalytic functions. Recently, the combined results of experiments that employ in vitro evolution methods, high-throughput sequencing and crystallographic structure determination have hinted at answers to these two questions: while the fitness landscape of ribozymes is rugged, meaning that their catalytic activity cannot be optimized by a smooth trajectory in sequence space, once an RNA achieves a stable three-dimensional fold, it can be endowed with distinctly different biochemical activities through small changes in genotype. This functional plasticity of highly structured RNAs may be particularly advantageous for the adaptation of organisms to drastic changes in selective pressure, or for the development of new biotechnological tools.http://www.mdpi.com/1420-3049/21/11/1570ribozymein vitro selectionfitness landscape |
| spellingShingle | Matthew W.L. Lau Adrian R. Ferré-D’Amaré Many Activities, One Structure: Functional Plasticity of Ribozyme Folds Molecules ribozyme in vitro selection fitness landscape |
| title | Many Activities, One Structure: Functional Plasticity of Ribozyme Folds |
| title_full | Many Activities, One Structure: Functional Plasticity of Ribozyme Folds |
| title_fullStr | Many Activities, One Structure: Functional Plasticity of Ribozyme Folds |
| title_full_unstemmed | Many Activities, One Structure: Functional Plasticity of Ribozyme Folds |
| title_short | Many Activities, One Structure: Functional Plasticity of Ribozyme Folds |
| title_sort | many activities one structure functional plasticity of ribozyme folds |
| topic | ribozyme in vitro selection fitness landscape |
| url | http://www.mdpi.com/1420-3049/21/11/1570 |
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