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LIS1 RNA-binding orchestrates the mechanosensitive properties of embryonic stem cells in AGO2-dependent and independent ways

Author

Listed:
  • Aditya Kshirsagar

    (Weizmann Institute of Science)

  • Svetlana Maslov Doroshev

    (Weizmann Institute of Science)

  • Anna Gorelik

    (Weizmann Institute of Science)

  • Tsviya Olender

    (Weizmann Institute of Science)

  • Tamar Sapir

    (Weizmann Institute of Science)

  • Daisuke Tsuboi

    (Fujita Health University)

  • Irit Rosenhek-Goldian

    (Weizmann Institute of Science)

  • Sergey Malitsky

    (Weizmann Institute of Science)

  • Maxim Itkin

    (Weizmann Institute of Science)

  • Amir Argoetti

    (Technion-Israel Institute of Technology)

  • Yael Mandel-Gutfreund

    (Technion-Israel Institute of Technology)

  • Sidney R. Cohen

    (Weizmann Institute of Science)

  • Jacob H. Hanna

    (Weizmann Institute of Science)

  • Igor Ulitsky

    (Weizmann Institute of Science)

  • Kozo Kaibuchi

    (Fujita Health University)

  • Orly Reiner

    (Weizmann Institute of Science)

Abstract

Lissencephaly-1 (LIS1) is associated with neurodevelopmental diseases and is known to regulate the molecular motor cytoplasmic dynein activity. Here we show that LIS1 is essential for the viability of mouse embryonic stem cells (mESCs), and it governs the physical properties of these cells. LIS1 dosage substantially affects gene expression, and we uncovered an unexpected interaction of LIS1 with RNA and RNA-binding proteins, most prominently the Argonaute complex. We demonstrate that LIS1 overexpression partially rescued the extracellular matrix (ECM) expression and mechanosensitive genes conferring stiffness to Argonaute null mESCs. Collectively, our data transforms the current perspective on the roles of LIS1 in post-transcriptional regulation underlying development and mechanosensitive processes.

Suggested Citation

  • Aditya Kshirsagar & Svetlana Maslov Doroshev & Anna Gorelik & Tsviya Olender & Tamar Sapir & Daisuke Tsuboi & Irit Rosenhek-Goldian & Sergey Malitsky & Maxim Itkin & Amir Argoetti & Yael Mandel-Gutfre, 2023. "LIS1 RNA-binding orchestrates the mechanosensitive properties of embryonic stem cells in AGO2-dependent and independent ways," Nature Communications, Nature, vol. 14(1), pages 1-21, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-38797-8
    DOI: 10.1038/s41467-023-38797-8
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