ArticlebioRxiv : the preprint server for biology2025
RNA virus polymerase-helicase coupling enables rapid elongation through duplex RNA.
Pim P B America, Subhas C Bera, Arnab Das, Thomas K Anderson, John C Marecki, Flávia S Papini, Jamie J Arnold, Robert N Kirchdoerfer, Craig E Cameron, Kevin D Raney and 2 more
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In one paragraphArticle in bioRxiv : the preprint server for biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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1 · What the graph read from itWhat it found
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5 · Who and what moneyAuthors and funding
12 authors.
Pim P B AmericaDepartment of Physics and Astronomy, and LaserLaB Amsterdam, Vrije Universiteit Amsterdam, De Boelelaan 1081, 1081 HV, Amsterdam, the Netherlands.ORCID 0000-0002-3977-376X Subhas C BeraJunior Research Group 2, Interdisciplinary Center for Clinical Research, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Cauerstr. 3, 91058 Erlangen, Germany.ORCID 0000-0002-4168-1805 Arnab DasDepartment of Physics and Astronomy, and LaserLaB Amsterdam, Vrije Universiteit Amsterdam, De Boelelaan 1081, 1081 HV, Amsterdam, the Netherlands.
Thomas K AndersonDepartment of Biochemistry and Institute for Molecular Virology, University of Wisconsin-Madison, Madison, WI 53706, USA.
John C MareckiDepartment of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.ORCID 0000-0003-1991-8949 Flávia S PapiniJunior Research Group 2, Interdisciplinary Center for Clinical Research, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Cauerstr. 3, 91058 Erlangen, Germany.
Jamie J ArnoldDepartment of Microbiology and Immunology, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.
Robert N KirchdoerferDepartment of Biochemistry and Institute for Molecular Virology, University of Wisconsin-Madison, Madison, WI 53706, USA.
Craig E CameronDepartment of Microbiology and Immunology, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.
Kevin D RaneyDepartment of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.ORCID 0000-0002-7290-0206 Martin DepkenDepartment of Bionanoscience, Kavli Institute of Nanoscience, Delft University of Technology, Van der Maasweg 9, 2629 HZ Delft, the Netherlands.ORCID 0000-0001-9194-6739 David DulinDepartment of Physics and Astronomy, and LaserLaB Amsterdam, Vrije Universiteit Amsterdam, De Boelelaan 1081, 1081 HV, Amsterdam, the Netherlands.ORCID 0000-0003-4209-0377 Funding
Research Project 1: Coronavirus antiviral lead development and combination testingU19AI171292 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI HEISE, MARK T · 2022 to 2022
$65.5MCoronavirus Genome ReplicationR01AI161841 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Jamie Jon Arnold, CRAIG E. CAMERON · 2021 to 2026
$3.4MCoronavirus RNA synthesis by multicomponent protein machinesR01AI158463 · NIAID · UNIVERSITY OF WISCONSIN-MADISON · PI KIRCHDOERFER, ROBERT N · 2020 to 2025
$2.1MNIAID NIH HHS R01 AI158463NIAID NIH HHS R01 AI161841NIAID NIH HHS U19 AI171292
6 · The paper itselfAbstract
Positive-sense (+) RNA viruses often encode helicases presumed to support replication. Their precise role remains unresolved though, especially in coronaviruses (CoV) where the helicase translocates in the opposite direction to the polymerase. Using high-throughput single-molecule magnetic tweezers, we show that the coronavirus helicase enhances RNA synthesis through duplex RNA by tenfold, forming a directional complex with the viral polymerase. Despite opposing polarity, the helicase coordinates elongation by engaging the non-template strand. A detailed kinetic model derived from large datasets reveals distinct dynamic states, including fast bursting and slow, backtracking-prone modes, which are governed by helicase engagement. These results uncover an active coupling mechanism that modulates replication dynamics and provide a mechanistic basis for continuous versus discontinuous RNA synthesis in coronaviruses. Our findings establish the viral helicase as a central regulator of RNA replication rather than a passive accessory enzyme.
Identifiers
PMID40093076
PMCPMC11908277
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