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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
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