Journal
RNA
Volume 28, Issue 2, Pages 239-249Publisher
COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
DOI: 10.1261/rna.078825.121
Keywords
COVID; RNA; base triple; near-atomic resolution; X-ray
Categories
Funding
- National Institute of General Medical Sciences of the National Institutes of Health (NIH) [P30 GM124165]
- NIH-ORIP HEI grant [S10OD021527]
- National Heart, Lung, and Blood Institute (NHLBI)
- NIH Intramural Targeted Anti-COVID-19 (ITAC) Program of the National Institute of Allergy and Infectious Diseases
- NHLBI, NIH
- [DE-AC02-06CH11357]
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SARS-CoV-2 uses a highly conserved RNA pseudoknot to enhance programmed -1 ribosomal frameshifting, resulting in the production of two viral protein precursors from one open reading frame. The 1.3 angstrom-resolution X-ray structure of the pseudoknot reveals three stacked helices supported by unique base triples, which could be targeted by potential small-molecule therapeutics.
SARS-CoV-2 produces two long viral protein precursors from one open reading frame using a highly conserved RNA pseudoknot that enhances programmed -1 ribosomal frameshifting. The 1.3 angstrom-resolution X-ray structure of the pseudoknot reveals three coaxially stacked helices buttressed by idiosyncratic base triples from loop residues. This structure represents a frameshift-stimulating state that must be deformed by the ribosome and exhibits base-triple-adjacent pockets that could be targeted by future small-molecule therapeutics.
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