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RBM15 condensates modulate m(6)A modification of STYK1 to promote tumorigenesis

RBM15 expression is recurrently upregulated in several types of malignant tissues, and its high expression level is typically associated with poor prognosis. However, whether and how RBM15 is involved in the tumor progression remains unclear. In this study, we found that overexpressing RBM15 in NIH3...

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Detalles Bibliográficos
Autores principales: Jiang, Amin, Zhang, Siwei, Wang, Xinyu, Li, Dong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Research Network of Computational and Structural Biotechnology 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9464649/
https://www.ncbi.nlm.nih.gov/pubmed/36147665
http://dx.doi.org/10.1016/j.csbj.2022.08.068
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author Jiang, Amin
Zhang, Siwei
Wang, Xinyu
Li, Dong
author_facet Jiang, Amin
Zhang, Siwei
Wang, Xinyu
Li, Dong
author_sort Jiang, Amin
collection PubMed
description RBM15 expression is recurrently upregulated in several types of malignant tissues, and its high expression level is typically associated with poor prognosis. However, whether and how RBM15 is involved in the tumor progression remains unclear. In this study, we found that overexpressing RBM15 in NIH3T3 cells was able to enhance proliferation rate in vitro and induced subcutaneous tumor formation in vivo. Moreover, we imaged the subcellular localization of RBM15 with our home-built structured illumination super-resolution microscopy, and revealed that RBM15 formed substantial condensates dispersed in the nucleus, undergoing dynamic fusion and fission activities. These condensates were partially colocalized with m(6)A-modified transcripts in the nucleus. In addition, we confirmed that RBM15 formed “liquid-like” droplets in a protein/salt concentration-dependent manner in vitro, and the addition of RNA further enhanced its phase-separation propensity. To identify downstream targets of RBM15, we performed meRIP-seq and RNA-seq, revealing that RBM15 preferentially bound to and promoted the m(6)A modification on the mRNA of Serine/threonine/tyrosine kinase 1 (STYK1), thereby enhancing its stability. The upregulated STYK1 expression caused MAPK hyperactivation, thereby leading to oncogenic transformation of NIH3T3 cells.
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spelling pubmed-94646492022-09-21 RBM15 condensates modulate m(6)A modification of STYK1 to promote tumorigenesis Jiang, Amin Zhang, Siwei Wang, Xinyu Li, Dong Comput Struct Biotechnol J Research Article RBM15 expression is recurrently upregulated in several types of malignant tissues, and its high expression level is typically associated with poor prognosis. However, whether and how RBM15 is involved in the tumor progression remains unclear. In this study, we found that overexpressing RBM15 in NIH3T3 cells was able to enhance proliferation rate in vitro and induced subcutaneous tumor formation in vivo. Moreover, we imaged the subcellular localization of RBM15 with our home-built structured illumination super-resolution microscopy, and revealed that RBM15 formed substantial condensates dispersed in the nucleus, undergoing dynamic fusion and fission activities. These condensates were partially colocalized with m(6)A-modified transcripts in the nucleus. In addition, we confirmed that RBM15 formed “liquid-like” droplets in a protein/salt concentration-dependent manner in vitro, and the addition of RNA further enhanced its phase-separation propensity. To identify downstream targets of RBM15, we performed meRIP-seq and RNA-seq, revealing that RBM15 preferentially bound to and promoted the m(6)A modification on the mRNA of Serine/threonine/tyrosine kinase 1 (STYK1), thereby enhancing its stability. The upregulated STYK1 expression caused MAPK hyperactivation, thereby leading to oncogenic transformation of NIH3T3 cells. Research Network of Computational and Structural Biotechnology 2022-09-05 /pmc/articles/PMC9464649/ /pubmed/36147665 http://dx.doi.org/10.1016/j.csbj.2022.08.068 Text en © 2022 The Author(s) https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Research Article
Jiang, Amin
Zhang, Siwei
Wang, Xinyu
Li, Dong
RBM15 condensates modulate m(6)A modification of STYK1 to promote tumorigenesis
title RBM15 condensates modulate m(6)A modification of STYK1 to promote tumorigenesis
title_full RBM15 condensates modulate m(6)A modification of STYK1 to promote tumorigenesis
title_fullStr RBM15 condensates modulate m(6)A modification of STYK1 to promote tumorigenesis
title_full_unstemmed RBM15 condensates modulate m(6)A modification of STYK1 to promote tumorigenesis
title_short RBM15 condensates modulate m(6)A modification of STYK1 to promote tumorigenesis
title_sort rbm15 condensates modulate m(6)a modification of styk1 to promote tumorigenesis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9464649/
https://www.ncbi.nlm.nih.gov/pubmed/36147665
http://dx.doi.org/10.1016/j.csbj.2022.08.068
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