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

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.

Metadata

Relations

Is version of: https://doi.org/10.1038/s41467-025-60084-x

DOI

https://doi.org/10.17192/openumr/855

Publisher

Springer Nature

Language

en

Data types

JournalArticle

Keywords

Gene regulation in immune cellsLong non-coding RNAsMonocytes and macrophagesSystems analysis

Funding

Funding Organisations:

Philipps-Universität Marburg

Project Information:Gefördert durch den Open-Access-Publikationsfonds der UB Marburg.

License

Attribution 4.0 International

URI

https://open.uni-marburg.de/handle/openumr/10837

Schmerer, Nils; Janga, Harshavardhan; Aillaud, Michelle; Hoffmann, Janina; Aznaourova, Marina; Wende, Sarah; Steding, Henrike; Halder, Luke Donald; Uhl, Michael; Boldt, Fabian; Stiewe, Thorsten; Nist, Andrea; Jerrentrup, Lukas; Kirschbaum, Andreas; Ruppert, Clemens; Rossbach, Oliver; Ntini, Evgenia; Marisco, Annalisa; Valasarajan, Chanil; Backofen, Rolf; Linne, Uwe; Pullamsetti, Soni S.; Schmeck, Bernd; Schulte, Leon: A searchable atlas of pathogen-sensitive lncRNA networks in human macrophages. In: Nature Communications, volume 16, Article number: 4733, Jg. (), S. 4733-4733. DOI: https://doi.org/10.17192/openumr/855.