LIS1 RNA-binding Orchestrates the Mechanosensitive Properties of Embryonic Stem Cells in AGO2-dependent and Independent Ways

Overview

Journal Nat Commun

Specialty Biology

Date 2023 Jun 6

PMID 37280197

Authors

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

Affiliations

Soon will be listed here.

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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