G3BP1 ribonucleoprotein complexes regulate focal adhesion protein mobility and cell migration

Summary: The subcellular localization of mRNAs plays a pivotal role in biological processes, including cell migration. For instance, β-actin mRNA and its associated RNA-binding protein (RBP), ZBP1/IGF2BP1, are recruited to focal adhesions (FAs) to support localized β-actin synthesis, crucial for cel...

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Main Authors: Liana C. Boraas, Mengwei Hu, Pieter Martino, Lauren Thornton, Charles E. Vejnar, Gang Zhen, Longhui Zeng, Dylan M. Parker, Andy L. Cox, Antonio J. Giraldez, Xiaolei Su, Christine Mayr, Siyuan Wang, Stefania Nicoli
Format: Article
Language:English
Published: Elsevier 2025-02-01
Series:Cell Reports
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Online Access:http://www.sciencedirect.com/science/article/pii/S2211124725000087
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author Liana C. Boraas
Mengwei Hu
Pieter Martino
Lauren Thornton
Charles E. Vejnar
Gang Zhen
Longhui Zeng
Dylan M. Parker
Andy L. Cox
Antonio J. Giraldez
Xiaolei Su
Christine Mayr
Siyuan Wang
Stefania Nicoli
author_facet Liana C. Boraas
Mengwei Hu
Pieter Martino
Lauren Thornton
Charles E. Vejnar
Gang Zhen
Longhui Zeng
Dylan M. Parker
Andy L. Cox
Antonio J. Giraldez
Xiaolei Su
Christine Mayr
Siyuan Wang
Stefania Nicoli
author_sort Liana C. Boraas
collection DOAJ
description Summary: The subcellular localization of mRNAs plays a pivotal role in biological processes, including cell migration. For instance, β-actin mRNA and its associated RNA-binding protein (RBP), ZBP1/IGF2BP1, are recruited to focal adhesions (FAs) to support localized β-actin synthesis, crucial for cell migration. However, whether other mRNAs and RBPs also localize at FAs remains unclear. Here, we identify hundreds of mRNAs that are enriched at FAs (FA-mRNAs). FA-mRNAs share characteristics with stress granule (SG) mRNAs and are found in ribonucleoprotein (RNP) complexes with the SG RBP. Mechanistically, G3BP1 binds to FA proteins in an RNA-dependent manner, and its RNA-binding and dimerization domains, essential for G3BP1 to form RNPs in SG, are required for FA localization and cell migration. We find that G3BP1 RNPs promote cell speed by enhancing FA protein mobility and FA size. These findings suggest a previously unappreciated role for G3BP1 RNPs in regulating FA function under non-stress conditions.
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issn 2211-1247
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publishDate 2025-02-01
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series Cell Reports
spelling doaj-art-c2203514e38d409cbbd92749fbad2d8d2025-01-30T05:14:01ZengElsevierCell Reports2211-12472025-02-01442115237G3BP1 ribonucleoprotein complexes regulate focal adhesion protein mobility and cell migrationLiana C. Boraas0Mengwei Hu1Pieter Martino2Lauren Thornton3Charles E. Vejnar4Gang Zhen5Longhui Zeng6Dylan M. Parker7Andy L. Cox8Antonio J. Giraldez9Xiaolei Su10Christine Mayr11Siyuan Wang12Stefania Nicoli13Yale Cardiovascular Research Center, Department of Internal Medicine, Section of Cardiology, Yale University School of Medicine, New Haven, CT 06511, USA; Department of Genetics, Yale University School of Medicine, New Haven, CT 06510, USA; Corresponding authorDepartment of Genetics, Yale University School of Medicine, New Haven, CT 06510, USAYale Cardiovascular Research Center, Department of Internal Medicine, Section of Cardiology, Yale University School of Medicine, New Haven, CT 06511, USA; Department of Genetics, Yale University School of Medicine, New Haven, CT 06510, USAYale Cardiovascular Research Center, Department of Internal Medicine, Section of Cardiology, Yale University School of Medicine, New Haven, CT 06511, USA; Department of Genetics, Yale University School of Medicine, New Haven, CT 06510, USADepartment of Genetics, Yale University School of Medicine, New Haven, CT 06510, USALaboratory of Genome Integrity, National Cancer Institute, NIH, Bethesda, MD 20892, USADepartment of Cell Biology, Yale University School of Medicine, New Haven, CT 06510, USA; Yale Cancer Center, Yale University, New Haven, CT, USADepartment of Biochemistry and Howard Hughes Medical Institute, University of Colorado Boulder, Boulder, CO, USADepartment of Genetics, Yale University School of Medicine, New Haven, CT 06510, USADepartment of Genetics, Yale University School of Medicine, New Haven, CT 06510, USADepartment of Cell Biology, Yale University School of Medicine, New Haven, CT 06510, USA; Yale Cancer Center, Yale University, New Haven, CT, USACancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center, New York, NY, USADepartment of Genetics, Yale University School of Medicine, New Haven, CT 06510, USA; Department of Cell Biology, Yale University School of Medicine, New Haven, CT 06510, USA; Corresponding authorYale Cardiovascular Research Center, Department of Internal Medicine, Section of Cardiology, Yale University School of Medicine, New Haven, CT 06511, USA; Department of Genetics, Yale University School of Medicine, New Haven, CT 06510, USA; Corresponding authorSummary: The subcellular localization of mRNAs plays a pivotal role in biological processes, including cell migration. For instance, β-actin mRNA and its associated RNA-binding protein (RBP), ZBP1/IGF2BP1, are recruited to focal adhesions (FAs) to support localized β-actin synthesis, crucial for cell migration. However, whether other mRNAs and RBPs also localize at FAs remains unclear. Here, we identify hundreds of mRNAs that are enriched at FAs (FA-mRNAs). FA-mRNAs share characteristics with stress granule (SG) mRNAs and are found in ribonucleoprotein (RNP) complexes with the SG RBP. Mechanistically, G3BP1 binds to FA proteins in an RNA-dependent manner, and its RNA-binding and dimerization domains, essential for G3BP1 to form RNPs in SG, are required for FA localization and cell migration. We find that G3BP1 RNPs promote cell speed by enhancing FA protein mobility and FA size. These findings suggest a previously unappreciated role for G3BP1 RNPs in regulating FA function under non-stress conditions.http://www.sciencedirect.com/science/article/pii/S2211124725000087CP: Cell biologyCP: Molecular biology
spellingShingle Liana C. Boraas
Mengwei Hu
Pieter Martino
Lauren Thornton
Charles E. Vejnar
Gang Zhen
Longhui Zeng
Dylan M. Parker
Andy L. Cox
Antonio J. Giraldez
Xiaolei Su
Christine Mayr
Siyuan Wang
Stefania Nicoli
G3BP1 ribonucleoprotein complexes regulate focal adhesion protein mobility and cell migration
Cell Reports
CP: Cell biology
CP: Molecular biology
title G3BP1 ribonucleoprotein complexes regulate focal adhesion protein mobility and cell migration
title_full G3BP1 ribonucleoprotein complexes regulate focal adhesion protein mobility and cell migration
title_fullStr G3BP1 ribonucleoprotein complexes regulate focal adhesion protein mobility and cell migration
title_full_unstemmed G3BP1 ribonucleoprotein complexes regulate focal adhesion protein mobility and cell migration
title_short G3BP1 ribonucleoprotein complexes regulate focal adhesion protein mobility and cell migration
title_sort g3bp1 ribonucleoprotein complexes regulate focal adhesion protein mobility and cell migration
topic CP: Cell biology
CP: Molecular biology
url http://www.sciencedirect.com/science/article/pii/S2211124725000087
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