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“Boundary residues” between the folded RNA recognition motif and disordered RGG domains are critical for FUS–RNA binding
Fused in sarcoma (FUS) is an abundant RNA-binding protein, which drives phase separation of cellular condensates and plays multiple roles in RNA regulation. The RNA-binding ability of FUS protein is crucial to its cellular function. Here, our molecular simulation study on the FUS–RNA complex provide...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society for Biochemistry and Molecular Biology
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10687056/ https://www.ncbi.nlm.nih.gov/pubmed/37890778 http://dx.doi.org/10.1016/j.jbc.2023.105392 |
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author | Balasubramanian, Sangeetha Maharana, Shovamayee Srivastava, Anand |
author_facet | Balasubramanian, Sangeetha Maharana, Shovamayee Srivastava, Anand |
author_sort | Balasubramanian, Sangeetha |
collection | PubMed |
description | Fused in sarcoma (FUS) is an abundant RNA-binding protein, which drives phase separation of cellular condensates and plays multiple roles in RNA regulation. The RNA-binding ability of FUS protein is crucial to its cellular function. Here, our molecular simulation study on the FUS–RNA complex provides atomic resolution insights into the observations from biochemical studies and also illuminates our understanding of molecular driving forces that mediate the structure, stability, and interaction of the RNA recognition motif (RRM) and RGG domains of FUS with a stem–loop junction RNA. We observe clear cooperativity and division of labor among the ordered (RRM) and disordered domains (RGG1 and RGG2) of FUS that leads to an organized and tighter RNA binding. Irrespective of the length of RGG2, the RGG2–RNA interaction is confined to the stem–loop junction and the proximal stem regions. On the other hand, the RGG1 interactions are primarily with the longer RNA stem. We find that the C terminus of RRM, which make up the “boundary residues” that connect the folded RRM with the long disordered RGG2 stretch of the protein, plays a critical role in FUS–RNA binding. Our study provides high-resolution molecular insights into the FUS–RNA interactions and forms the basis for understanding the molecular origins of full-length FUS interaction with RNA. |
format | Online Article Text |
id | pubmed-10687056 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | American Society for Biochemistry and Molecular Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-106870562023-11-30 “Boundary residues” between the folded RNA recognition motif and disordered RGG domains are critical for FUS–RNA binding Balasubramanian, Sangeetha Maharana, Shovamayee Srivastava, Anand J Biol Chem Research Article Fused in sarcoma (FUS) is an abundant RNA-binding protein, which drives phase separation of cellular condensates and plays multiple roles in RNA regulation. The RNA-binding ability of FUS protein is crucial to its cellular function. Here, our molecular simulation study on the FUS–RNA complex provides atomic resolution insights into the observations from biochemical studies and also illuminates our understanding of molecular driving forces that mediate the structure, stability, and interaction of the RNA recognition motif (RRM) and RGG domains of FUS with a stem–loop junction RNA. We observe clear cooperativity and division of labor among the ordered (RRM) and disordered domains (RGG1 and RGG2) of FUS that leads to an organized and tighter RNA binding. Irrespective of the length of RGG2, the RGG2–RNA interaction is confined to the stem–loop junction and the proximal stem regions. On the other hand, the RGG1 interactions are primarily with the longer RNA stem. We find that the C terminus of RRM, which make up the “boundary residues” that connect the folded RRM with the long disordered RGG2 stretch of the protein, plays a critical role in FUS–RNA binding. Our study provides high-resolution molecular insights into the FUS–RNA interactions and forms the basis for understanding the molecular origins of full-length FUS interaction with RNA. American Society for Biochemistry and Molecular Biology 2023-10-27 /pmc/articles/PMC10687056/ /pubmed/37890778 http://dx.doi.org/10.1016/j.jbc.2023.105392 Text en © 2023 The Authors https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Research Article Balasubramanian, Sangeetha Maharana, Shovamayee Srivastava, Anand “Boundary residues” between the folded RNA recognition motif and disordered RGG domains are critical for FUS–RNA binding |
title | “Boundary residues” between the folded RNA recognition motif and disordered RGG domains are critical for FUS–RNA binding |
title_full | “Boundary residues” between the folded RNA recognition motif and disordered RGG domains are critical for FUS–RNA binding |
title_fullStr | “Boundary residues” between the folded RNA recognition motif and disordered RGG domains are critical for FUS–RNA binding |
title_full_unstemmed | “Boundary residues” between the folded RNA recognition motif and disordered RGG domains are critical for FUS–RNA binding |
title_short | “Boundary residues” between the folded RNA recognition motif and disordered RGG domains are critical for FUS–RNA binding |
title_sort | “boundary residues” between the folded rna recognition motif and disordered rgg domains are critical for fus–rna binding |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10687056/ https://www.ncbi.nlm.nih.gov/pubmed/37890778 http://dx.doi.org/10.1016/j.jbc.2023.105392 |
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