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Peer-reviewedCC BYNature communications

RNA binding proteome profiling reveals RNA-dependent activation of oncogenic host signaling during KSHV infection.

  • Yang Zhao1,2,3,4
  • Xiang Ye1,2,3,4
  • Madeline Yuen1
  • Ruilin Zhang1,2,3
  • W Hayes McDonald5,6
  • John Karijolich7,8,9,10,11
11 affiliations
  1. 1Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA.
  2. 2Vanderbilt Center for Immunobiology, Nashville, TN, USA.
  3. 3Vanderbilt Institute for Infection, Immunology, and Inflammation, Nashville, TN, USA.
  4. 4Vanderbilt Ingram Cancer Center, Nashville, TN, USA.
  5. 5Department of Biochemistry, Vanderbilt University, Nashville, TN, USA.
  6. 6Mass Spectrometry Research Center, Vanderbilt University, Nashville, TN, USA.
  7. 7Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA. [email protected].
  8. 8Vanderbilt Center for Immunobiology, Nashville, TN, USA. [email protected].
  9. 9Vanderbilt Institute for Infection, Immunology, and Inflammation, Nashville, TN, USA. [email protected].
  10. 10Vanderbilt Ingram Cancer Center, Nashville, TN, USA. [email protected].
  11. 11Department of Biochemistry, Vanderbilt University, Nashville, TN, USA. [email protected].
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Abstract

Viruses encode RNA-binding proteins (RBPs) to manipulate host processes and promote infection. However, due to limited genomic space, many viral proteins are multifunctional and may engage RNA through non-canonical domains, making their identification difficult using traditional sequence-based approaches. Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiological agent of many AIDS-associated cancers. Here, leveraging an unbiased proteomic approach we identified all RBPs in KSHV-infected primary effusion lymphoma (PEL) cells, uncovering 7 previously unrecognized KSHV-encoded RBPs. Among these is viral Interferon Regulatory Factor 1 (vIRF1), which we found is both necessary and sufficient to activate oncogenic RAS/MAPK signaling through an RNA-dependent interaction with host G3BP proteins. Importantly, a KSHV vIRF1 mutant lacking the ability to bind RNA exhibits a B cell-specific replication defect, highlighting the essential role of RNA interactions in viral gene regulation and pathogenesis. These findings reveal a novel strategy by which KSHV hijacks RNA-mediated signaling to support its lifecycle.

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Cite

BibTeXRIS
BibTeX
@article{zhao2026binding,
  title = {{RNA binding proteome profiling reveals RNA-dependent activation of oncogenic host signaling during KSHV infection.}},
  author = {Yang Zhao and Xiang Ye and Madeline Yuen and Ruilin Zhang and W Hayes McDonald and John Karijolich},
  journal = {Nature communications},
  year = {2026},
  month = sep,
  doi = {10.1038/s41467-026-77861-x},
  url = {https://europepmc.org/article/MED/42894007},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - RNA binding proteome profiling reveals RNA-dependent activation of oncogenic host signaling during KSHV infection.
AU  - Yang Zhao
AU  - Xiang Ye
AU  - Madeline Yuen
AU  - Ruilin Zhang
AU  - W Hayes McDonald
AU  - John Karijolich
PY  - 2026
DA  - 2026/09/16
JO  - Nature communications
DO  - 10.1038/s41467-026-77861-x
UR  - https://europepmc.org/article/MED/42894007
AB  - Viruses encode RNA-binding proteins (RBPs) to manipulate host processes and promote infection. However, due to limited genomic space, many viral proteins are multifunctional and may engage RNA through non-canonical domains, making their identification difficult using traditional sequence-based approaches. Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiological agent of many AIDS-associated cancers. Here, leveraging an unbiased proteomic approach we identified all RBPs in KSHV-infected primary effusion lymphoma (PEL) cells, uncovering 7 previously unrecognized KSHV-encoded RBPs. Among these is viral Interferon Regulatory Factor 1 (vIRF1), which we found is both necessary and sufficient to activate oncogenic RAS/MAPK signaling through an RNA-dependent interaction with host G3BP proteins. Importantly, a KSHV vIRF1 mutant lacking the ability to bind RNA exhibits a B cell-specific replication defect, highlighting the essential role of RNA interactions in viral gene regulation and pathogenesis. These findings reveal a novel strategy by which KSHV hijacks RNA-mediated signaling to support its lifecycle.
SN  - 2041-1723
ER  -