IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-30322-7.html
   My bibliography  Save this article

HDLBP binds ER-targeted mRNAs by multivalent interactions to promote protein synthesis of transmembrane and secreted proteins

Author

Listed:
  • Ulrike Zinnall

    (Berlin Institute for Medical Systems Biology)

  • Miha Milek

    (Berlin Institute for Medical Systems Biology
    National Institute of Chemistry
    Berlin Institute of Health at Charité)

  • Igor Minia

    (Berlin Institute for Medical Systems Biology)

  • Carlos H. Vieira-Vieira

    (Berlin Institute for Medical Systems Biology)

  • Simon Müller

    (Martin Luther University)

  • Guido Mastrobuoni

    (Berlin Institute for Medical Systems Biology)

  • Orsalia-Georgia Hazapis

    (Berlin Institute for Medical Systems Biology)

  • Simone Giudice

    (Berlin Institute for Medical Systems Biology)

  • David Schwefel

    (Charite-Universitätsmedizin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institute of Medical Physics and Biophysics)

  • Nadine Bley

    (Martin Luther University)

  • Franka Voigt

    (Friedrich Miescher Institute for Biomedical Research)

  • Jeffrey A. Chao

    (Friedrich Miescher Institute for Biomedical Research)

  • Stefan Kempa

    (Berlin Institute for Medical Systems Biology)

  • Stefan Hüttelmaier

    (Martin Luther University)

  • Matthias Selbach

    (Berlin Institute for Medical Systems Biology
    Charite-Universitätsmedizin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institute of Medical Physics and Biophysics)

  • Markus Landthaler

    (Berlin Institute for Medical Systems Biology
    Humboldt-Universität zu Berlin)

Abstract

The biological role of RNA-binding proteins in the secretory pathway is not well established. Here, we describe that human HDLBP/Vigilin directly interacts with more than 80% of ER-localized mRNAs. PAR-CLIP analysis reveals that these transcripts represent high affinity HDLBP substrates and are specifically bound in their coding sequences (CDS), in contrast to CDS/3’UTR-bound cytosolic mRNAs. HDLBP crosslinks strongly to long CU-rich motifs, which frequently reside in CDS of ER-localized mRNAs and result in high affinity multivalent interactions. In addition to HDLBP-ncRNA interactome, quantification of HDLBP-proximal proteome confirms association with components of the translational apparatus and the signal recognition particle. Absence of HDLBP results in decreased translation efficiency of HDLBP target mRNAs, impaired protein synthesis and secretion in model cell lines, as well as decreased tumor growth in a lung cancer mouse model. These results highlight a general function for HDLBP in the translation of ER-localized mRNAs and its relevance for tumor progression.

Suggested Citation

  • Ulrike Zinnall & Miha Milek & Igor Minia & Carlos H. Vieira-Vieira & Simon Müller & Guido Mastrobuoni & Orsalia-Georgia Hazapis & Simone Giudice & David Schwefel & Nadine Bley & Franka Voigt & Jeffrey, 2022. "HDLBP binds ER-targeted mRNAs by multivalent interactions to promote protein synthesis of transmembrane and secreted proteins," Nature Communications, Nature, vol. 13(1), pages 1-21, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-30322-7
    DOI: 10.1038/s41467-022-30322-7
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-30322-7
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-022-30322-7?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. Naama Aviram & Tslil Ast & Elizabeth A. Costa & Eric C. Arakel & Silvia G. Chuartzman & Calvin H. Jan & Sarah Haßdenteufel & Johanna Dudek & Martin Jung & Stefan Schorr & Richard Zimmermann & Blanche , 2016. "The SND proteins constitute an alternative targeting route to the endoplasmic reticulum," Nature, Nature, vol. 540(7631), pages 134-138, December.
    2. Anton A. Polyansky & Mario Hlevnjak & Bojan Zagrovic, 2013. "Analogue encoding of physicochemical properties of proteins in their cognate messenger RNAs," Nature Communications, Nature, vol. 4(1), pages 1-11, December.
    3. Justin W. Chartron & Katherine C. L. Hunt & Judith Frydman, 2016. "Cotranslational signal-independent SRP preloading during membrane targeting," Nature, Nature, vol. 536(7615), pages 224-228, August.
    4. Debashish Ray & Hilal Kazan & Kate B. Cook & Matthew T. Weirauch & Hamed S. Najafabadi & Xiao Li & Serge Gueroussov & Mihai Albu & Hong Zheng & Ally Yang & Hong Na & Manuel Irimia & Leah H. Matzat & R, 2013. "A compendium of RNA-binding motifs for decoding gene regulation," Nature, Nature, vol. 499(7457), pages 172-177, July.
    5. Mehrpouya B. Mobin & Stefanie Gerstberger & Daniel Teupser & Benedetta Campana & Klaus Charisse & Markus H. Heim & Muthiah Manoharan & Thomas Tuschl & Markus Stoffel, 2016. "The RNA-binding protein vigilin regulates VLDL secretion through modulation of Apob mRNA translation," Nature Communications, Nature, vol. 7(1), pages 1-13, November.
    6. Andreas M. Anger & Jean-Paul Armache & Otto Berninghausen & Michael Habeck & Marion Subklewe & Daniel N. Wilson & Roland Beckmann, 2013. "Structures of the human and Drosophila 80S ribosome," Nature, Nature, vol. 497(7447), pages 80-85, May.
    Full references (including those not matched with items on IDEAS)

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Patricia Álvarez-Campos & Helena García-Castro & Elena Emili & Alberto Pérez-Posada & Irene Olmo & Sophie Peron & David A. Salamanca-Díaz & Vincent Mason & Bria Metzger & Alexandra E. Bely & Nathan J., 2024. "Annelid adult cell type diversity and their pluripotent cellular origins," Nature Communications, Nature, vol. 15(1), pages 1-22, December.

    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. Xuan Ye & Wen Yang & Soon Yi & Yanan Zhao & Gabriele Varani & Eckhard Jankowsky & Fan Yang, 2023. "Two distinct binding modes provide the RNA-binding protein RbFox with extraordinary sequence specificity," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    2. Melanie A. McDowell & Michael Heimes & Giray Enkavi & Ákos Farkas & Daniel Saar & Klemens Wild & Blanche Schwappach & Ilpo Vattulainen & Irmgard Sinning, 2023. "The GET insertase exhibits conformational plasticity and induces membrane thinning," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    3. Kai Hao & Yawen Chen & Xiumin Yan & Xueliang Zhu, 2021. "Cilia locally synthesize proteins to sustain their ultrastructure and functions," Nature Communications, Nature, vol. 12(1), pages 1-16, December.
    4. Ryan Damme & Kongpan Li & Minjie Zhang & Jianhui Bai & Wilson H. Lee & Joseph D. Yesselman & Zhipeng Lu & Willem A. Velema, 2022. "Chemical reversible crosslinking enables measurement of RNA 3D distances and alternative conformations in cells," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    5. Claudia M. Fusco & Kristina Desch & Aline R. Dörrbaum & Mantian Wang & Anja Staab & Ivy C. W. Chan & Eleanor Vail & Veronica Villeri & Julian D. Langer & Erin M. Schuman, 2021. "Neuronal ribosomes exhibit dynamic and context-dependent exchange of ribosomal proteins," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
    6. Yue Liu & Yue Yang & Chenying Xu & Jianxing Liu & Jiale Chen & Guoqing Li & Bin Huang & Yi Pan & Yanfeng Zhang & Qiong Wei & Stephen J. Pandol & Fangfang Zhang & Ling Li & Liang Jin, 2023. "Circular RNA circGlis3 protects against islet β-cell dysfunction and apoptosis in obesity," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    7. Patrick C. Hoffmann & Jan Philipp Kreysing & Iskander Khusainov & Maarten W. Tuijtel & Sonja Welsch & Martin Beck, 2022. "Structures of the eukaryotic ribosome and its translational states in situ," Nature Communications, Nature, vol. 13(1), pages 1-9, December.
    8. Aidan M. Fenix & Yuichiro Miyaoka & Alessandro Bertero & Steven M. Blue & Matthew J. Spindler & Kenneth K. B. Tan & Juan A. Perez-Bermejo & Amanda H. Chan & Steven J. Mayerl & Trieu D. Nguyen & Caitli, 2021. "Gain-of-function cardiomyopathic mutations in RBM20 rewire splicing regulation and re-distribute ribonucleoprotein granules within processing bodies," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
    9. Thu Giang Nguyen & Christina Ritter & Eva Kummer, 2023. "Structural insights into the role of GTPBP10 in the RNA maturation of the mitoribosome," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    10. Seungjae Lee & Yen-Chung Chen & Austin E. Gillen & J. Matthew Taliaferro & Bart Deplancke & Hongjie Li & Eric C. Lai, 2022. "Diverse cell-specific patterns of alternative polyadenylation in Drosophila," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    11. Huijuan Feng & Xiang-Jun Lu & Suvrajit Maji & Linxi Liu & Dmytro Ustianenko & Noam D. Rudnick & Chaolin Zhang, 2024. "Structure-based prediction and characterization of photo-crosslinking in native protein–RNA complexes," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    12. Yan Chen & Bin Tsai & Ningning Li & Ning Gao, 2022. "Structural remodeling of ribosome associated Hsp40-Hsp70 chaperones during co-translational folding," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    13. Patrick R. Smith & Sarah Loerch & Nikesh Kunder & Alexander D. Stanowick & Tzu-Fang Lou & Zachary T. Campbell, 2021. "Functionally distinct roles for eEF2K in the control of ribosome availability and p-body abundance," Nature Communications, Nature, vol. 12(1), pages 1-16, December.
    14. Deivid C. Rodrigues & Marat Mufteev & Kyoko E. Yuki & Ashrut Narula & Wei Wei & Alina Piekna & Jiajie Liu & Peter Pasceri & Olivia S. Rissland & Michael D. Wilson & James Ellis, 2023. "Buffering of transcription rate by mRNA half-life is a conserved feature of Rett syndrome models," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    15. Seisuke Yamashita & Kozo Tomita, 2023. "Mechanism of U6 snRNA oligouridylation by human TUT1," Nature Communications, Nature, vol. 14(1), pages 1-10, December.
    16. Christoph Sadée & Lauren D. Hagler & Winston R. Becker & Inga Jarmoskaite & Pavanapuresan P. Vaidyanathan & Sarah K. Denny & William J. Greenleaf & Daniel Herschlag, 2022. "A comprehensive thermodynamic model for RNA binding by the Saccharomyces cerevisiae Pumilio protein PUF4," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    17. Maya Ron & Igor Ulitsky, 2022. "Context-specific effects of sequence elements on subcellular localization of linear and circular RNAs," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    18. Lukas Bartonek & Bojan Zagrovic, 2017. "mRNA/protein sequence complementarity and its determinants: The impact of affinity scales," PLOS Computational Biology, Public Library of Science, vol. 13(7), pages 1-16, July.
    19. Jordan Currie & Vyshnavi Manda & Sean K. Robinson & Celine Lai & Vertica Agnihotri & Veronica Hidalgo & R. W. Ludwig & Kai Zhang & Jay Pavelka & Zhao V. Wang & June-Wha Rhee & Maggie P. Y. Lam & Edwar, 2024. "Simultaneous proteome localization and turnover analysis reveals spatiotemporal features of protein homeostasis disruptions," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    20. Siddharth Sethi & David Zhang & Sebastian Guelfi & Zhongbo Chen & Sonia Garcia-Ruiz & Emmanuel O. Olagbaju & Mina Ryten & Harpreet Saini & Juan A. Botia, 2022. "Leveraging omic features with F3UTER enables identification of unannotated 3’UTRs for synaptic genes," Nature Communications, Nature, vol. 13(1), pages 1-15, 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:13:y:2022:i:1:d:10.1038_s41467-022-30322-7. 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.