IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v16y2025i1d10.1038_s41467-025-60084-x.html
   My bibliography  Save this article

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
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-025-60084-x
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-025-60084-x?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Chung-Chau Hon & Jordan A. Ramilowski & Jayson Harshbarger & Nicolas Bertin & Owen J. L. Rackham & Julian Gough & Elena Denisenko & Sebastian Schmeier & Thomas M. Poulsen & Jessica Severin & Marina Li, 2017. "An atlas of human long non-coding RNAs with accurate 5′ ends," Nature, Nature, vol. 543(7644), pages 199-204, March.
    2. Eric L. Nostrand & Peter Freese & Gabriel A. Pratt & Xiaofeng Wang & Xintao Wei & Rui Xiao & Steven M. Blue & Jia-Yu Chen & Neal A. L. Cody & Daniel Dominguez & Sara Olson & Balaji Sundararaman & Liju, 2020. "A large-scale binding and functional map of human RNA-binding proteins," Nature, Nature, vol. 583(7818), pages 711-719, July.
    3. Sarah Djebali & Carrie A. Davis & Angelika Merkel & Alex Dobin & Timo Lassmann & Ali Mortazavi & Andrea Tanzer & Julien Lagarde & Wei Lin & Felix Schlesinger & Chenghai Xue & Georgi K. Marinov & Jaina, 2012. "Landscape of transcription in human cells," Nature, Nature, vol. 489(7414), pages 101-108, September.
    4. Antonella Managò & Valentina Audrito & Francesca Mazzola & Leonardo Sorci & Federica Gaudino & Katiuscia Gizzi & Nicoletta Vitale & Danny Incarnato & Gabriele Minazzato & Alice Ianniello & Antonio Var, 2019. "Extracellular nicotinate phosphoribosyltransferase binds Toll like receptor 4 and mediates inflammation," Nature Communications, Nature, vol. 10(1), pages 1-14, December.
    5. Shiuli Agarwal & Tim Vierbuchen & Sreya Ghosh & Jennie Chan & Zhaozhao Jiang & Richard K. Kandasamy & Emiliano Ricci & Katherine A. Fitzgerald, 2020. "The long non-coding RNA LUCAT1 is a negative feedback regulator of interferon responses in humans," Nature Communications, Nature, vol. 11(1), pages 1-11, December.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Wei Hu & Yangjun Wu & Qili Shi & Jingni Wu & Deping Kong & Xiaohua Wu & Xianghuo He & Teng Liu & Shengli Li, 2022. "Systematic characterization of cancer transcriptome at transcript resolution," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    2. Matvei Khoroshkin & Andrey Buyan & Martin Dodel & Albertas Navickas & Johnny Yu & Fathima Trejo & Anthony Doty & Rithvik Baratam & Shaopu Zhou & Sean B. Lee & Tanvi Joshi & Kristle Garcia & Benedict C, 2024. "Systematic identification of post-transcriptional regulatory modules," Nature Communications, Nature, vol. 15(1), pages 1-21, December.
    3. Haofan Sun & Bin Fu & Xiaohong Qian & Ping Xu & Weijie Qin, 2024. "Nuclear and cytoplasmic specific RNA binding proteome enrichment and its changes upon ferroptosis induction," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    4. Wojciech Barczak & Simon M. Carr & Geng Liu & Shonagh Munro & Annalisa Nicastri & Lian Ni Lee & Claire Hutchings & Nicola Ternette & Paul Klenerman & Alexander Kanapin & Anastasia Samsonova & Nicholas, 2023. "Long non-coding RNA-derived peptides are immunogenic and drive a potent anti-tumour response," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    5. Timofey A. Karginov & Antoine Ménoret & Anthony T. Vella, 2022. "Optimal CD8+ T cell effector function requires costimulation-induced RNA-binding proteins that reprogram the transcript isoform landscape," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    6. Letizia Pitto & Francesca Gorini & Fabrizio Bianchi & Elena Guzzolino, 2020. "New Insights into Mechanisms of Endocrine-Disrupting Chemicals in Thyroid Diseases: The Epigenetic Way," IJERPH, MDPI, vol. 17(21), pages 1-18, October.
    7. Edie-Rosmin Wu & Ming-Ju Hsieh & Whei-Ling Chiang & Kuan-Chun Hsueh & Shun-Fa Yang & Shih-Chi Su, 2019. "Association of lncRNA CCAT2 and CASC8 Gene Polymorphisms with Hepatocellular Carcinoma," IJERPH, MDPI, vol. 16(16), pages 1-11, August.
    8. Anna Knörlein & Chris P. Sarnowski & Tebbe Vries & Moritz Stoltz & Michael Götze & Ruedi Aebersold & Frédéric H.-T. Allain & Alexander Leitner & Jonathan Hall, 2022. "Nucleotide-amino acid π-stacking interactions initiate photo cross-linking in RNA-protein complexes," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    9. Amir Argoetti & Dor Shalev & Galia Polyak & Noa Shima & Hadas Biran & Tamar Lahav & Tamar Hashimshony & Yael Mandel-Gutfreund, 2025. "lncRNA NORAD modulates STAT3/STAT1 balance and innate immune responses in human cells via interaction with STAT3," Nature Communications, Nature, vol. 16(1), pages 1-14, December.
    10. Miquel Anglada-Girotto & Ludovica Ciampi & Sophie Bonnal & Sarah A. Head & Samuel Miravet-Verde & Luis Serrano, 2024. "In silico RNA isoform screening to identify potential cancer driver exons with therapeutic applications," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    11. Zhantao Shao & Jack Hu & Allison Jandura & Ronit Wilk & Matthew Jachimowicz & Lingfeng Ma & Chun Hu & Abby Sundquist & Indrani Das & Phillip Samuel-Larbi & Julie A. Brill & Henry M. Krause, 2024. "Spatially revealed roles for lncRNAs in Drosophila spermatogenesis, Y chromosome function and evolution," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    12. Johanna Luige & Alexandros Armaos & Gian Gaetano Tartaglia & Ulf Andersson Vang Ørom, 2024. "Predicting nuclear G-quadruplex RNA-binding proteins with roles in transcription and phase separation," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    13. Sarah E. Harris & Maria S. Alexis & Gilbert Giri & Francisco F. Cavazos & Yue Hu & Jernej Murn & Maria M. Aleman & Christopher B. Burge & Daniel Dominguez, 2024. "Understanding species-specific and conserved RNA-protein interactions in vivo and in vitro," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    14. Zhao Wang & Qian Liang & Xinyi Qian & Bolang Hu & Zhanye Zheng & Jianhua Wang & Yuelin Hu & Zhengkai Bao & Ke Zhao & Yao Zhou & Xiangling Feng & Xianfu Yi & Jin Li & Jiandang Shi & Zhe Liu & Jihui Hao, 2023. "An autoimmune pleiotropic SNP modulates IRF5 alternative promoter usage through ZBTB3-mediated chromatin looping," Nature Communications, Nature, vol. 14(1), pages 1-23, December.
    15. Xiusheng Zhu & Lei Huang & Chao Wang & Guoli Li & Biao Deng & Dashuai Kong & Xiaoxiao Wang & Rongrong Chang & Yi Gu & Qiuhan Wen & Siyuan Kong & Yuwen Liu & Yubo Zhang, 2025. "Uncovering the whole genome silencers of human cells via Ss-STARR-seq," Nature Communications, Nature, vol. 16(1), pages 1-16, December.
    16. Anne-Emmanuelle Foucher & Leila Touat-Todeschini & Ariadna B. Juarez-Martinez & Auriane Rakitch & Hamida Laroussi & Claire Karczewski & Samira Acajjaoui & Montserrat Soler-López & Stephen Cusack & Cam, 2022. "Structural analysis of Red1 as a conserved scaffold of the RNA-targeting MTREC/PAXT complex," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    17. Chirag Nepal & Jesper B. Andersen, 2023. "Alternative promoters in CpG depleted regions are prevalently associated with epigenetic misregulation of liver cancer transcriptomes," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    18. Tamar Sapir & Aditya Kshirsagar & Anna Gorelik & Tsviya Olender & Ziv Porat & Ingrid E. Scheffer & David B. Goldstein & Orrin Devinsky & Orly Reiner, 2022. "Heterogeneous nuclear ribonucleoprotein U (HNRNPU) safeguards the developing mouse cortex," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    19. Erika Schaudy & Kathrin Hölz & Jory Lietard & Mark M. Somoza, 2022. "Simple synthesis of massively parallel RNA microarrays via enzymatic conversion from DNA microarrays," Nature Communications, Nature, vol. 13(1), pages 1-9, December.
    20. Mariela Cortés-López & Laura Schulz & Mihaela Enculescu & Claudia Paret & Bea Spiekermann & Mathieu Quesnel-Vallières & Manuel Torres-Diz & Sebastian Unic & Anke Busch & Anna Orekhova & Monika Kuban &, 2022. "High-throughput mutagenesis identifies mutations and RNA-binding proteins controlling CD19 splicing and CART-19 therapy resistance," Nature Communications, Nature, vol. 13(1), pages 1-17, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-60084-x. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.