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10.1021/jacs.1c03003

http://scihub22266oqcxt.onion/10.1021/jacs.1c03003
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34283611!8315264!34283611
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suck abstract from ncbi


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pmid34283611      J+Am+Chem+Soc 2021 ; 143 (30): 11404-11422
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  • To Knot or Not to Knot: Multiple Conformations of the SARS-CoV-2 Frameshifting RNA Element #MMPMID34283611
  • Schlick T; Zhu Q; Dey A; Jain S; Yan S; Laederach A
  • J Am Chem Soc 2021[Aug]; 143 (30): 11404-11422 PMID34283611show ga
  • The SARS-CoV-2 frameshifting RNA element (FSE) is an excellent target for therapeutic intervention against Covid-19. This small gene element employs a shifting mechanism to pause and backtrack the ribosome during translation between Open Reading Frames 1a and 1b, which code for viral polyproteins. Any interference with this process has a profound effect on viral replication and propagation. Pinpointing the structures adapted by the FSE and associated structural transformations involved in frameshifting has been a challenge. Using our graph-theory-based modeling tools for representing RNA secondary structures, "RAG" (RNA-As-Graphs), and chemical structure probing experiments, we show that the 3-stem H-type pseudoknot (3_6 dual graph), long assumed to be the dominant structure, has a viable alternative, an HL-type 3-stem pseudoknot (3_3) for longer constructs. In addition, an unknotted 3-way junction RNA (3_5) emerges as a minor conformation. These three conformations share Stems 1 and 3, while the different Stem 2 may be involved in a conformational switch and possibly associations with the ribosome during translation. For full-length genomes, a stem-loop motif (2_2) may compete with these forms. These structural and mechanistic insights advance our understanding of the SARS-CoV-2 frameshifting process and concomitant virus life cycle, and point to three avenues of therapeutic intervention.
  • |Base Sequence[MESH]
  • |Inverted Repeat Sequences[MESH]
  • |Models, Molecular[MESH]
  • |Nucleic Acid Conformation[MESH]
  • |RNA, Viral/*chemistry/genetics[MESH]


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