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<p>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.</p>

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

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年5月21日

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  • Nils Schmerer,
  • Harshavardhan Janga,
  • Michelle Aillaud,
  • Janina Hoffmann,
  • Marina Aznaourova,
  • Sarah Wende,
  • Henrike Steding,
  • Luke D. Halder,
  • Michael Uhl,
  • Fabian Boldt,
  • Thorsten Stiewe,
  • Andrea Nist,
  • Lukas Jerrentrup,
  • Andreas Kirschbaum,
  • Clemens Ruppert,
  • Oliver Rossbach,
  • Evgenia Ntini,
  • Annalisa Marsico,
  • Chanil Valasarajan,
  • Rolf Backofen,
  • Uwe Linne,
  • Soni S. Pullamsetti,
  • Bernd Schmeck,
  • Leon N. Schulte

摘要

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.