A conserved class of viral RNA structures regulates translation reinitiation through dynamic ribosome interactions
Summary: Certain viral RNAs encode proteins downstream of their main open reading frame, expressed through “termination-reinitiation” events. In some cases, structures located upstream of the first stop codon within these viral RNAs bind the ribosome, inhibiting ribosome recycling and inducing reini...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-02-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124725000075 |
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| author | Madeline E. Sherlock Conner J. Langeberg Katherine E. Segar Jeffrey S. Kieft |
| author_facet | Madeline E. Sherlock Conner J. Langeberg Katherine E. Segar Jeffrey S. Kieft |
| author_sort | Madeline E. Sherlock |
| collection | DOAJ |
| description | Summary: Certain viral RNAs encode proteins downstream of their main open reading frame, expressed through “termination-reinitiation” events. In some cases, structures located upstream of the first stop codon within these viral RNAs bind the ribosome, inhibiting ribosome recycling and inducing reinitiation. We used bioinformatics methods to identify new examples of viral reinitiation-stimulating RNAs and experimentally verified their secondary structure and function. We determined the structure of a representative viral RNA-ribosome complex using cryoelectron microscopy (cryo-EM). 3D classification and variability analyses reveal that the viral RNA structure can sample a range of conformations while remaining tethered to the ribosome, enabling the ribosome to find a reinitiation start site within a limited range of mRNA sequence. Evaluating the conserved features and constraints of this entire RNA class within the context of the cryo-EM reconstruction provides insight into mechanisms enabling reinitiation, a translation regulation strategy employed by many other viral and eukaryotic systems. |
| format | Article |
| id | doaj-art-744ff700f36b46a89ac3495b17b7680a |
| institution | Kabale University |
| issn | 2211-1247 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj-art-744ff700f36b46a89ac3495b17b7680a2025-02-03T04:16:39ZengElsevierCell Reports2211-12472025-02-01442115236A conserved class of viral RNA structures regulates translation reinitiation through dynamic ribosome interactionsMadeline E. Sherlock0Conner J. Langeberg1Katherine E. Segar2Jeffrey S. Kieft3Department of Biochemistry and Molecular Genetics, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USADepartment of Biochemistry and Molecular Genetics, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USADepartment of Biochemistry and Molecular Genetics, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USADepartment of Biochemistry and Molecular Genetics, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; Corresponding authorSummary: Certain viral RNAs encode proteins downstream of their main open reading frame, expressed through “termination-reinitiation” events. In some cases, structures located upstream of the first stop codon within these viral RNAs bind the ribosome, inhibiting ribosome recycling and inducing reinitiation. We used bioinformatics methods to identify new examples of viral reinitiation-stimulating RNAs and experimentally verified their secondary structure and function. We determined the structure of a representative viral RNA-ribosome complex using cryoelectron microscopy (cryo-EM). 3D classification and variability analyses reveal that the viral RNA structure can sample a range of conformations while remaining tethered to the ribosome, enabling the ribosome to find a reinitiation start site within a limited range of mRNA sequence. Evaluating the conserved features and constraints of this entire RNA class within the context of the cryo-EM reconstruction provides insight into mechanisms enabling reinitiation, a translation regulation strategy employed by many other viral and eukaryotic systems.http://www.sciencedirect.com/science/article/pii/S2211124725000075CP: Molecular biology |
| spellingShingle | Madeline E. Sherlock Conner J. Langeberg Katherine E. Segar Jeffrey S. Kieft A conserved class of viral RNA structures regulates translation reinitiation through dynamic ribosome interactions Cell Reports CP: Molecular biology |
| title | A conserved class of viral RNA structures regulates translation reinitiation through dynamic ribosome interactions |
| title_full | A conserved class of viral RNA structures regulates translation reinitiation through dynamic ribosome interactions |
| title_fullStr | A conserved class of viral RNA structures regulates translation reinitiation through dynamic ribosome interactions |
| title_full_unstemmed | A conserved class of viral RNA structures regulates translation reinitiation through dynamic ribosome interactions |
| title_short | A conserved class of viral RNA structures regulates translation reinitiation through dynamic ribosome interactions |
| title_sort | conserved class of viral rna structures regulates translation reinitiation through dynamic ribosome interactions |
| topic | CP: Molecular biology |
| url | http://www.sciencedirect.com/science/article/pii/S2211124725000075 |
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