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A searchable atlas of pathogen-sensitive lncRNA networks in human macrophages

Author

Listed:
  • Nils Schmerer

    (Philipps University Marburg)

  • Harshavardhan Janga

    (Philipps University Marburg)

  • Michelle Aillaud

    (Philipps University Marburg)

  • Janina Hoffmann

    (Philipps University Marburg)

  • Marina Aznaourova

    (Philipps University Marburg)

  • Sarah Wende

    (Philipps University Marburg)

  • Henrike Steding

    (Philipps University Marburg)

  • Luke D. Halder

    (Philipps University Marburg)

  • Michael Uhl

    (University of Freiburg
    University of Freiburg)

  • Fabian Boldt

    (Philipps University Marburg)

  • Thorsten Stiewe

    (German Center for Lung Research (DZL)
    University of Marburg
    Justus-Liebig University)

  • Andrea Nist

    (University of Marburg)

  • Lukas Jerrentrup

    (Philipps University Marburg)

  • Andreas Kirschbaum

    (University Hospital Giessen and Marburg (UKGM))

  • Clemens Ruppert

    (German Center for Lung Research (DZL)
    Universities of Giessen and Marburg Lung Center (UGMLC)
    UGMLC Giessen Biobank and european IPF registry (eurIPFreg))

  • Oliver Rossbach

    (Justus Liebig University Giessen)

  • Evgenia Ntini

    (Max Planck Institute for Molecular Genetics)

  • Annalisa Marsico

    (Max Planck Institute for Molecular Genetics
    Helmholtz Center)

  • Chanil Valasarajan

    (Universities of Giessen and Marburg Lung Center (UGMLC)
    Max Planck Institute for Heart and Lung Research
    Justus-Liebig University)

  • Rolf Backofen

    (University of Freiburg
    University of Freiburg)

  • Uwe Linne

    (Philipps University)

  • Soni S. Pullamsetti

    (German Center for Lung Research (DZL)
    Justus-Liebig University
    Universities of Giessen and Marburg Lung Center (UGMLC)
    Max Planck Institute for Heart and Lung Research)

  • Bernd Schmeck

    (Philipps University Marburg
    German Center for Lung Research (DZL)
    Justus-Liebig University
    Philipps University Marburg)

  • Leon N. Schulte

    (Philipps University Marburg
    German Center for Lung Research (DZL))

Abstract

Long noncoding RNAs (lncRNA) are crucial yet underexplored regulators of human immunity. Here we develop GRADR, a method integrating gradient profiling with RNA-binding proteome analysis, to map the protein interactomes of all expressed RNAs in a single experiment to study mechanisms of lncRNA-mediated regulation of human primary macrophages. Applying GRADR alongside CRISPR-multiomics, we reveal a network of NFκB-dependent lncRNAs, including LINC01215, AC022816.1 and ROCKI, which modulate distinct aspects of macrophage immunity, particularly through interactions with mRNA-processing factors, such as hnRNP proteins. We further uncover the function of ROCKI in repressing the messenger of the anti-inflammatory GATA2 transcription factor, thus promoting macrophage activation. Lastly, all data are consolidated in the SMyLR web interface, a searchable reference catalog for exploring lncRNA functions and pathway-dependencies in immune cells. Our results thus not only highlight the important functions of lncRNAs in immune regulation, but also provide a rich resource for lncRNA studies.

Suggested Citation

  • Nils Schmerer & Harshavardhan Janga & Michelle Aillaud & Janina Hoffmann & Marina Aznaourova & Sarah Wende & Henrike Steding & Luke D. Halder & Michael Uhl & Fabian Boldt & Thorsten Stiewe & Andrea Ni, 2025. "A searchable atlas of pathogen-sensitive lncRNA networks in human macrophages," Nature Communications, Nature, vol. 16(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-60084-x
    DOI: 10.1038/s41467-025-60084-x
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