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Browsing by Person "Becker, Matthias Alexander"

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    Biophysical characterization of the conformational landscape underlying SARS-CoV-2 RNA genome circularization
    2026-04-20
    Becker, Matthias Alexander
    Robio, Zineb
    Richter, Christian 
    Wacker, Anna
    Stirnal, Elke
    Witt, Kerstin
    Schwalbe, Harald Jochen 
    RNA viruses possess strictly conserved RNA segments that adopt local structures and act as regulatory cis-acting elements. In addition, long-range RNA-RNA interactions between distant parts of their genome add additional layers of regulatory control. In SARS-CoV-2, crosslinking experiments identified multiple transiently formed long-range interactions within its genome. The longest distance interaction occurs between nucleotides in the 5’- and the 3’-terminal, untranslated regions (UTR’s). Their interaction requires opening of the 5’SL3 element that contains the transcription regulatory core sequence (TRS-L) in the 5’-UTR and of the 3’SL3base element in the 3’-UTR. In this study, we investigate the minimal sequence context necessary for formation of this long-range interaction. We determine alternative secondary structures formed by these elements, their thermodynamic stability and the stability of individual base-pairs. Further, we quantify populations and kinetic parameters in a three-strand equilibrium between the circularized form and the alternative structures formed within the UTR’s. We demonstrate that the stability of circularization is significantly reduced in subgenomic RNAs, pointing at a role of circularization in differentiating between genomic and subgenomic RNA during the viral life cycle.
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