IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-39135-8.html
   My bibliography  Save this article

In vivo PAR-CLIP (viP-CLIP) of liver TIAL1 unveils targets regulating cholesterol synthesis and secretion

Author

Listed:
  • Hasan Vatandaslar

    (ETH Zurich)

  • Aitor Garzia

    (The Rockefeller University)

  • Cindy Meyer

    (The Rockefeller University)

  • Svenja Godbersen

    (ETH Zurich)

  • Laura T. L. Brandt

    (ETH Zurich)

  • Esther Griesbach

    (Friedrich Miescher Institute for Biomedical Research)

  • Jeffrey A. Chao

    (Friedrich Miescher Institute for Biomedical Research)

  • Thomas Tuschl

    (The Rockefeller University)

  • Markus Stoffel

    (ETH Zurich
    University of Zürich)

Abstract

System-wide cross-linking and immunoprecipitation (CLIP) approaches have unveiled regulatory mechanisms of RNA-binding proteins (RBPs) mainly in cultured cells due to limitations in the cross-linking efficiency of tissues. Here, we describe viP-CLIP (in vivo PAR-CLIP), a method capable of identifying RBP targets in mammalian tissues, thereby facilitating the functional analysis of RBP-regulatory networks in vivo. We applied viP-CLIP to mouse livers and identified Insig2 and ApoB as prominent TIAL1 target transcripts, indicating an important role of TIAL1 in cholesterol synthesis and secretion. The functional relevance of these targets was confirmed by showing that TIAL1 influences their translation in hepatocytes. Mutant Tial1 mice exhibit altered cholesterol synthesis, APOB secretion and plasma cholesterol levels. Our results demonstrate that viP-CLIP can identify physiologically relevant RBP targets by finding a factor implicated in the negative feedback regulation of cholesterol biosynthesis.

Suggested Citation

  • Hasan Vatandaslar & Aitor Garzia & Cindy Meyer & Svenja Godbersen & Laura T. L. Brandt & Esther Griesbach & Jeffrey A. Chao & Thomas Tuschl & Markus Stoffel, 2023. "In vivo PAR-CLIP (viP-CLIP) of liver TIAL1 unveils targets regulating cholesterol synthesis and secretion," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-39135-8
    DOI: 10.1038/s41467-023-39135-8
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-39135-8
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-023-39135-8?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. Jürgen Soutschek & Akin Akinc & Birgit Bramlage & Klaus Charisse & Rainer Constien & Mary Donoghue & Sayda Elbashir & Anke Geick & Philipp Hadwiger & Jens Harborth & Matthias John & Venkitasamy Kesava, 2004. "Therapeutic silencing of an endogenous gene by systemic administration of modified siRNAs," Nature, Nature, vol. 432(7014), pages 173-178, November.
    2. Björn Schwanhäusser & Dorothea Busse & Na Li & Gunnar Dittmar & Johannes Schuchhardt & Jana Wolf & Wei Chen & Matthias Selbach, 2011. "Global quantification of mammalian gene expression control," Nature, Nature, vol. 473(7347), pages 337-342, May.
    3. Tracy S. Zimmermann & Amy C. H. Lee & Akin Akinc & Birgit Bramlage & David Bumcrot & Matthew N. Fedoruk & Jens Harborth & James A. Heyes & Lloyd B. Jeffs & Matthias John & Adam D. Judge & Kieu Lam & K, 2006. "RNAi-mediated gene silencing in non-human primates," Nature, Nature, vol. 441(7089), pages 111-114, May.
    4. Toby Mathieson & Holger Franken & Jan Kosinski & Nils Kurzawa & Nico Zinn & Gavain Sweetman & Daniel Poeckel & Vikram S. Ratnu & Maike Schramm & Isabelle Becher & Michael Steidel & Kyung-Min Noh & Gio, 2018. "Systematic analysis of protein turnover in primary cells," Nature Communications, Nature, vol. 9(1), pages 1-10, December.
    5. Masashi Yamaji & Miki Jishage & Cindy Meyer & Hemant Suryawanshi & Evan Der & Misaki Yamaji & Aitor Garzia & Pavel Morozov & Sudhir Manickavel & Hannah L. McFarland & Robert G. Roeder & Markus Hafner , 2017. "DND1 maintains germline stem cells via recruitment of the CCR4–NOT complex to target mRNAs," Nature, Nature, vol. 543(7646), pages 568-572, March.
    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. Ji Min Lee & Henrik M. Hammarén & Mikhail M. Savitski & Sung Hee Baek, 2023. "Control of protein stability by post-translational modifications," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    2. Yuping Chen & Jo-Hsi Huang & Connie Phong & James E. Ferrell, 2024. "Viscosity-dependent control of protein synthesis and degradation," Nature Communications, Nature, vol. 15(1), pages 1-11, December.
    3. Gábor Csárdi & Alexander Franks & David S Choi & Edoardo M Airoldi & D Allan Drummond, 2015. "Accounting for Experimental Noise Reveals That mRNA Levels, Amplified by Post-Transcriptional Processes, Largely Determine Steady-State Protein Levels in Yeast," PLOS Genetics, Public Library of Science, vol. 11(5), pages 1-32, May.
    4. Simone Sanzo & Katrin Spengler & Anja Leheis & Joanna M. Kirkpatrick & Theresa L. Rändler & Tim Baldensperger & Therese Dau & Christian Henning & Luca Parca & Christian Marx & Zhao-Qi Wang & Marcus A., 2021. "Mapping protein carboxymethylation sites provides insights into their role in proteostasis and cell proliferation," Nature Communications, Nature, vol. 12(1), pages 1-22, December.
    5. Henrik M. Hammarén & Eva-Maria Geissen & Clement M. Potel & Martin Beck & Mikhail M. Savitski, 2022. "Protein-Peptide Turnover Profiling reveals the order of PTM addition and removal during protein maturation," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    6. Kaslik, Eva & Rădulescu, Ileana Rodica, 2022. "Stability and bifurcations in fractional-order gene regulatory networks," Applied Mathematics and Computation, Elsevier, vol. 421(C).
    7. Suran Kim & Sungjin Min & Yi Sun Choi & Sung-Hyun Jo & Jae Hun Jung & Kyusun Han & Jin Kim & Soohwan An & Yong Woo Ji & Yun-Gon Kim & Seung-Woo Cho, 2022. "Tissue extracellular matrix hydrogels as alternatives to Matrigel for culturing gastrointestinal organoids," Nature Communications, Nature, vol. 13(1), pages 1-21, December.
    8. Lingling Li & Dongxian Jiang & Qiao Zhang & Hui Liu & Fujiang Xu & Chunmei Guo & Zhaoyu Qin & Haixing Wang & Jinwen Feng & Yang Liu & Weijie Chen & Xue Zhang & Lin Bai & Sha Tian & Subei Tan & Chen Xu, 2023. "Integrative proteogenomic characterization of early esophageal cancer," Nature Communications, Nature, vol. 14(1), pages 1-28, December.
    9. Thomas C. J. Tan & Van Kelly & Xiaoyan Zou & David Wright & Tony Ly & Rose Zamoyska, 2022. "Translation factor eIF5a is essential for IFNγ production and cell cycle regulation in primary CD8+ T lymphocytes," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    10. Katharina Clemm von Hohenberg & Sandra Müller & Sibylle Schleich & Matthias Meister & Jonathan Bohlen & Thomas G. Hofmann & Aurelio A. Teleman, 2022. "Cyclin B/CDK1 and Cyclin A/CDK2 phosphorylate DENR to promote mitotic protein translation and faithful cell division," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    11. Jonathan J. Swietlik & Stefanie Bärthel & Chiara Falcomatà & Diana Fink & Ankit Sinha & Jingyuan Cheng & Stefan Ebner & Peter Landgraf & Daniela C. Dieterich & Henrik Daub & Dieter Saur & Felix Meissn, 2023. "Cell-selective proteomics segregates pancreatic cancer subtypes by extracellular proteins in tumors and circulation," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    12. Ryosuke Ishimura & Afnan H. El-Gowily & Daisuke Noshiro & Satoko Komatsu-Hirota & Yasuko Ono & Mayumi Shindo & Tomohisa Hatta & Manabu Abe & Takefumi Uemura & Hyeon-Cheol Lee-Okada & Tarek M. Mohamed , 2022. "The UFM1 system regulates ER-phagy through the ufmylation of CYB5R3," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    13. Sébastien Durand & Marion Bruelle & Fleur Bourdelais & Bigitha Bennychen & Juliana Blin-Gonthier & Caroline Isaac & Aurélia Huyghe & Sylvie Martel & Antoine Seyve & Christophe Vanbelle & Annie Adrait , 2023. "RSL24D1 sustains steady-state ribosome biogenesis and pluripotency translational programs in embryonic stem cells," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    14. Malgorzata M. Duszczyk & Harry Wischnewski & Tamara Kazeeva & Rajika Arora & Fionna E. Loughlin & Christine Schroetter & Ugo Pradère & Jonathan Hall & Constance Ciaudo & Frédéric H.-T. Allain, 2022. "The solution structure of Dead End bound to AU-rich RNA reveals an unusual mode of tandem RRM-RNA recognition required for mRNA regulation," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    15. Rune B Jakobsen & Esben Østrup & Xiaolan Zhang & Tarjei S Mikkelsen & Jan E Brinchmann, 2014. "Analysis of the Effects of Five Factors Relevant to In Vitro Chondrogenesis of Human Mesenchymal Stem Cells Using Factorial Design and High Throughput mRNA-Profiling," PLOS ONE, Public Library of Science, vol. 9(5), pages 1-13, May.
    16. Beatrice T. Laudenbach & Karsten Krey & Quirin Emslander & Line Lykke Andersen & Alexander Reim & Pietro Scaturro & Sarah Mundigl & Christopher Dächert & Katrin Manske & Markus Moser & Janos Ludwig & , 2021. "NUDT2 initiates viral RNA degradation by removal of 5′-phosphates," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
    17. McNutt Patrick & Hubbard Kyle & Beske Phil & Gut Ian, 2015. "A novel method to prioritize RNAseq data for post-hoc analysis based on absolute changes in transcript abundance," Statistical Applications in Genetics and Molecular Biology, De Gruyter, vol. 14(3), pages 227-241, June.
    18. Elena Grahn & Svenja V. Kaufmann & Malika Askarova & Momchil Ninov & Luisa M. Welp & Thomas K. Berger & Henning Urlaub & U.Benjamin Kaupp, 2023. "Control of intracellular pH and bicarbonate by CO2 diffusion into human sperm," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    19. Kaushik Bhattacharya & Samarpan Maiti & Szabolcs Zahoran & Lorenz Weidenauer & Dina Hany & Diana Wider & Lilia Bernasconi & Manfredo Quadroni & Martine Collart & Didier Picard, 2022. "Translational reprogramming in response to accumulating stressors ensures critical threshold levels of Hsp90 for mammalian life," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    20. Feng Yuan & Yi Li & Xinyue Zhou & Peiyuan Meng & Peng Zou, 2023. "Spatially resolved mapping of proteome turnover dynamics with subcellular precision," Nature Communications, Nature, vol. 14(1), pages 1-13, 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:14:y:2023:i:1:d:10.1038_s41467-023-39135-8. 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.