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; Orly Reiner

doi:https://doi.org/10.1038/s41467-023-38797-8

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, Orly Reiner

Weizmann Institute of Science, Technion - Israel Institute of Technology

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Article number	3293
Number of pages	21
Journal	Nature Communications
Volume	14
Issue number	1
DOIs	https://doi.org/10.1038/s41467-023-38797-8
State	Published - Jun 2023

All Science Journal Classification (ASJC) codes

General Chemistry
General Biochemistry,Genetics and Molecular Biology
General Physics and Astronomy

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Kshirsagar, A., Doroshev, S. M., Gorelik, A., Olender, T., Sapir, T., Tsuboi, D., Rosenhek-Goldian, I., Malitsky, S., Itkin, M., Argoetti, A., Mandel-Gutfreund, Y., Cohen, S. R., Hanna, J. H., Ulitsky, I., Kaibuchi, K., & Reiner, O. (2023). LIS1 RNA-binding orchestrates the mechanosensitive properties of embryonic stem cells in AGO2-dependent and independent ways. Nature Communications, 14(1), Article 3293. https://doi.org/10.1038/s41467-023-38797-8

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

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.",

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

note = "Publisher Copyright: {\textcopyright} 2023, The Author(s).",

year = "2023",

month = jun,

doi = "https://doi.org/10.1038/s41467-023-38797-8",

language = "الإنجليزيّة",

volume = "14",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Publishing Group",

number = "1",

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Kshirsagar, A, Doroshev, SM, Gorelik, A, Olender, T, Sapir, T, Tsuboi, D, Rosenhek-Goldian, I, Malitsky, S, Itkin, M, Argoetti, A, Mandel-Gutfreund, Y, Cohen, SR, Hanna, JH , Ulitsky, I, Kaibuchi, K & Reiner, O 2023, 'LIS1 RNA-binding orchestrates the mechanosensitive properties of embryonic stem cells in AGO2-dependent and independent ways', Nature Communications, vol. 14, no. 1, 3293. https://doi.org/10.1038/s41467-023-38797-8

TY - JOUR

T1 - LIS1 RNA-binding orchestrates the mechanosensitive properties of embryonic stem cells in AGO2-dependent and independent ways

AU - Kshirsagar, Aditya

AU - Doroshev, Svetlana Maslov

AU - Gorelik, Anna

AU - Olender, Tsviya

AU - Sapir, Tamar

AU - Tsuboi, Daisuke

AU - Rosenhek-Goldian, Irit

AU - Malitsky, Sergey

AU - Itkin, Maxim

AU - Argoetti, Amir

AU - Mandel-Gutfreund, Yael

AU - Cohen, Sidney R.

AU - Hanna, Jacob H.

AU - Ulitsky, Igor

AU - Kaibuchi, Kozo

AU - Reiner, Orly

PY - 2023/6

Y1 - 2023/6

N2 - 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.

AB - 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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DO - https://doi.org/10.1038/s41467-023-38797-8

M3 - مقالة

C2 - 37280197

SN - 2041-1723

VL - 14

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 3293

ER -

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

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