Vault RNAs aid RNA virus infection by facilitating cytoplasmic localization of hnRNP C and ELAVL1

  • Cell Rep. 2025 Jun 24;44(6):115823. doi: 10.1016/j.celrep.2025.115823.
Jorn E Stok  1 ,  Sander B van der Kooij  1 ,  Dennis Gravekamp  1 ,  Laurens R Ter Haar  1 ,  Jasper W de Wolf  1 ,  Clarisse Salgado-Benvindo  2 ,  Tessa Nelemans  2 ,  Bart J M Grijmans  1 ,  Rayman T N Tjokrodirijo  3 ,  Arnoud H de Ru  3 ,  Peter A van Veelen  3 ,  Martijn J van Hemert  2 ,  Marjolein Kikkert  2 ,  Annemarthe G van der Veen  4
Affiliations
  • 1. Leiden University Medical Center, Department of Immunology, Leiden, the Netherlands.
  • 2. Leiden University Medical Center, Leiden University Center for Infectious Diseases, Leiden, the Netherlands.
  • 3. Leiden University Medical Center, Center for Proteomics and Metabolomics, Leiden, the Netherlands.
  • 4. Leiden University Medical Center, Department of Immunology, Leiden, the Netherlands. Electronic address: [email protected].
PMID: 40512618 DOI: 10.1016/j.celrep.2025.115823
Abstract

Vault RNAs (vtRNAs) are a family of four small non-coding RNAs that regulate multiple cellular pathways in human cells. VtRNA expression is increased upon Infection with certain RNA and DNA viruses, suggesting that they either promote or restrict viral replication. However, their precise molecular function remains unclear. We show that replication of picornaviruses, alphaviruses, and beta-coronaviruses broadly enhances vtRNA expression. Genetic loss of vtRNAs inhibits replication of Sindbis virus (SINV) and encephalomyocarditis virus (EMCV), independent of the Antiviral type I interferon response. A proteomic screen demonstrates that vtRNAs associate with RNA-binding proteins ELAVL1 and hnRNP C in uninfected and infected cells. During Infection, vtRNAs facilitate cytoplasmic localization of ELAVL1 and hnRNP C, where these proteins associate with viral RNA and support SINV replication. Together, our findings reveal a proviral function of vtRNAs during SINV and EMCV Infection, which presents therapeutic opportunities to fight infectious diseases.

Keywords
CP: Microbiology; CP: Molecular biology; ELAVL1; RNA-binding proteins; hnRNP C; host-pathogen interaction; small non-coding RNA; vault RNA; vtRNA.
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