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

Autor: 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, Orly Reiner
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Nature Communications, Vol 14, Iss 1, Pp 1-21 (2023)
Druh dokumentu: article
ISSN: 2041-1723
DOI: 10.1038/s41467-023-38797-8
Popis: 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.
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