RNA virus polymerase-helicase coupling enables rapid elongation through duplex RNA

America PP, Bera SC, Das A, Anderson TK, Marecki JC, Papini FS, Arnold JJ, Kirchdoerfer RN, Cameron CE, Raney KD, Depken M, Dulin D (2026)

Publication Type: Journal article

Publication year: 2026

Journal

Cell Reports Elsevier (Cell Press)

Book Volume: 45

Article Number: 117273

Journal Issue: 4

DOI: 10.1016/j.celrep.2026.117273

Abstract

SummaryPositive-sense RNA ((+)RNA) viruses often encode helicases presumed to support replication. Their precise role remains unresolved, though, especially in coronaviruses (CoVs), 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 10-fold, forming a directional complex with the viral polymerase. Despite opposing polarity, the helicase coordinates elongation by engaging with 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.

Authors with CRIS profile

Subhas Chandra Bera Interdisziplinäres Zentrum für Klinische Forschung IZKF Nachwuchsgruppe 2 Prof. Dr. Dulin David Dulin Interdisziplinäres Zentrum für Klinische Forschung IZKF Nachwuchsgruppe 2 Prof. Dr. Dulin

Involved external institutions

University of Arkansas for Medical Sciences (UAMS) US United States (USA) (US) Delft University of Technology (TU Delft) NL Netherlands (NL) University of Wisconsin - Madison US United States (USA) (US) University of North Carolina at Chapel Hill US United States (USA) (US)

How to cite

APA:

America, P.P., Bera, S.C., Das, A., Anderson, T.K., Marecki, J.C., Papini, F.S.,... Dulin, D. (2026). RNA virus polymerase-helicase coupling enables rapid elongation through duplex RNA. Cell Reports, 45(4). https://doi.org/10.1016/j.celrep.2026.117273

MLA:

America, Pim P.B., et al. "RNA virus polymerase-helicase coupling enables rapid elongation through duplex RNA." Cell Reports 45.4 (2026).

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