Programmed −1 ribosomal frameshifting from the perspective of the conformational dynamics of mRNA and ribosomes
Programmed −1 ribosomal frameshifting (−1 PRF) is a translation mechanism that regulates the relative expression level of two proteins encoded on the same messenger RNA (mRNA). This regulation is commonly used by viruses such as coronaviruses and retroviruses but rarely by host human cells, and for...
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| Format: | Article |
| Language: | English |
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Elsevier
2021-01-01
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| Series: | Computational and Structural Biotechnology Journal |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2001037021002531 |
| _version_ | 1818950506724196352 |
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| author | Kai-Chun Chang Jin-Der Wen |
| author_facet | Kai-Chun Chang Jin-Der Wen |
| author_sort | Kai-Chun Chang |
| collection | DOAJ |
| description | Programmed −1 ribosomal frameshifting (−1 PRF) is a translation mechanism that regulates the relative expression level of two proteins encoded on the same messenger RNA (mRNA). This regulation is commonly used by viruses such as coronaviruses and retroviruses but rarely by host human cells, and for this reason, it has long been considered as a therapeutic target for antiviral drug development. Understanding the molecular mechanism of −1 PRF is one step toward this goal. Minus-one PRF occurs with a certain efficiency when translating ribosomes encounter the specialized mRNA signal consisting of the frameshifting site and a downstream stimulatory structure, which impedes translocation of the ribosome. The impeded ribosome can still undergo profound conformational changes to proceed with translocation; however, some of these changes may be unique and essential to frameshifting. In addition, most stimulatory structures exhibit conformational dynamics and sufficient mechanical strength, which, when under the action of ribosomes, may in turn further promote −1 PRF efficiency. In this review, we discuss how the dynamic features of ribosomes and mRNA stimulatory structures may influence the occurrence of −1 PRF and propose a hypothetical frameshifting model that recapitulates the role of conformational dynamics. |
| first_indexed | 2024-12-20T09:19:41Z |
| format | Article |
| id | doaj.art-47f276e003b8488c951485d29d30537b |
| institution | Directory Open Access Journal |
| issn | 2001-0370 |
| language | English |
| last_indexed | 2024-12-20T09:19:41Z |
| publishDate | 2021-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Computational and Structural Biotechnology Journal |
| spelling | doaj.art-47f276e003b8488c951485d29d30537b2022-12-21T19:45:19ZengElsevierComputational and Structural Biotechnology Journal2001-03702021-01-011935803588Programmed −1 ribosomal frameshifting from the perspective of the conformational dynamics of mRNA and ribosomesKai-Chun Chang0Jin-Der Wen1Department of Bioengineering and Therapeutic Sciences, Schools of Medicine and Pharmacy, University of California, San Francisco, CA 94158, United StatesInstitute of Molecular and Cellular Biology, National Taiwan University, Taipei 10617, Taiwan; Genome and Systems Biology Degree Program, National Taiwan University and Academia Sinica, Taipei 10617, Taiwan; Corresponding author at: Institute of Molecular and Cellular Biology, National Taiwan University, Taipei 10617, Taiwan.Programmed −1 ribosomal frameshifting (−1 PRF) is a translation mechanism that regulates the relative expression level of two proteins encoded on the same messenger RNA (mRNA). This regulation is commonly used by viruses such as coronaviruses and retroviruses but rarely by host human cells, and for this reason, it has long been considered as a therapeutic target for antiviral drug development. Understanding the molecular mechanism of −1 PRF is one step toward this goal. Minus-one PRF occurs with a certain efficiency when translating ribosomes encounter the specialized mRNA signal consisting of the frameshifting site and a downstream stimulatory structure, which impedes translocation of the ribosome. The impeded ribosome can still undergo profound conformational changes to proceed with translocation; however, some of these changes may be unique and essential to frameshifting. In addition, most stimulatory structures exhibit conformational dynamics and sufficient mechanical strength, which, when under the action of ribosomes, may in turn further promote −1 PRF efficiency. In this review, we discuss how the dynamic features of ribosomes and mRNA stimulatory structures may influence the occurrence of −1 PRF and propose a hypothetical frameshifting model that recapitulates the role of conformational dynamics.http://www.sciencedirect.com/science/article/pii/S2001037021002531Ribosomal frameshiftingSingle-moleculeOptical tweezerssmFRETMD simulationCryo-EM |
| spellingShingle | Kai-Chun Chang Jin-Der Wen Programmed −1 ribosomal frameshifting from the perspective of the conformational dynamics of mRNA and ribosomes Computational and Structural Biotechnology Journal Ribosomal frameshifting Single-molecule Optical tweezers smFRET MD simulation Cryo-EM |
| title | Programmed −1 ribosomal frameshifting from the perspective of the conformational dynamics of mRNA and ribosomes |
| title_full | Programmed −1 ribosomal frameshifting from the perspective of the conformational dynamics of mRNA and ribosomes |
| title_fullStr | Programmed −1 ribosomal frameshifting from the perspective of the conformational dynamics of mRNA and ribosomes |
| title_full_unstemmed | Programmed −1 ribosomal frameshifting from the perspective of the conformational dynamics of mRNA and ribosomes |
| title_short | Programmed −1 ribosomal frameshifting from the perspective of the conformational dynamics of mRNA and ribosomes |
| title_sort | programmed 1 ribosomal frameshifting from the perspective of the conformational dynamics of mrna and ribosomes |
| topic | Ribosomal frameshifting Single-molecule Optical tweezers smFRET MD simulation Cryo-EM |
| url | http://www.sciencedirect.com/science/article/pii/S2001037021002531 |
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