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

Aditya Kshirsagar, Svetlana Maslov Doroshev, Anna Gorelik, Tsviya Olender, Tamar Sapir, Daisuke Tsuboi, Irit Rosenhek-Goldian, Sergey Malitsky, Maxim Itkin, Amir Argoetti, Yael Mandel-Gutfreund, Sidney R. Cohen, Jacob H. Hanna, Igor Ulitsky, Kozo Kaibuchi and Orly Reiner ()
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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

Nature Communications, 2023, vol. 14, issue 1, 1-21

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41467-023-38797-8

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