RBM15 condensates modulate m6A 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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Elsevier
2022-01-01
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| Series: | Computational and Structural Biotechnology Journal |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2001037022004020 |
| _version_ | 1797978147325476864 |
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| author | Amin Jiang Siwei Zhang Xinyu Wang Dong Li |
| author_facet | Amin Jiang Siwei Zhang Xinyu Wang Dong Li |
| author_sort | Amin Jiang |
| collection | DOAJ |
| 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 m6A-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 m6A 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. |
| first_indexed | 2024-04-11T05:19:25Z |
| format | Article |
| id | doaj.art-4e05d07919724b3fa92b51c819d59c58 |
| institution | Directory Open Access Journal |
| issn | 2001-0370 |
| language | English |
| last_indexed | 2024-04-11T05:19:25Z |
| publishDate | 2022-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Computational and Structural Biotechnology Journal |
| spelling | doaj.art-4e05d07919724b3fa92b51c819d59c582022-12-24T04:54:18ZengElsevierComputational and Structural Biotechnology Journal2001-03702022-01-012048254836RBM15 condensates modulate m6A modification of STYK1 to promote tumorigenesisAmin Jiang0Siwei Zhang1Xinyu Wang2Dong Li3School of Life Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230026, China; National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, ChinaNational Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, ChinaNational Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; Corresponding authors at: National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China (X. Wang and D. Li).National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; College of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, China; Corresponding authors at: National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China (X. Wang and D. Li).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 m6A-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 m6A 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.http://www.sciencedirect.com/science/article/pii/S2001037022004020RBM15N6-methyladenine modificationPhase separationSTYK1 |
| spellingShingle | Amin Jiang Siwei Zhang Xinyu Wang Dong Li RBM15 condensates modulate m6A modification of STYK1 to promote tumorigenesis Computational and Structural Biotechnology Journal RBM15 N6-methyladenine modification Phase separation STYK1 |
| title | RBM15 condensates modulate m6A modification of STYK1 to promote tumorigenesis |
| title_full | RBM15 condensates modulate m6A modification of STYK1 to promote tumorigenesis |
| title_fullStr | RBM15 condensates modulate m6A modification of STYK1 to promote tumorigenesis |
| title_full_unstemmed | RBM15 condensates modulate m6A modification of STYK1 to promote tumorigenesis |
| title_short | RBM15 condensates modulate m6A modification of STYK1 to promote tumorigenesis |
| title_sort | rbm15 condensates modulate m6a modification of styk1 to promote tumorigenesis |
| topic | RBM15 N6-methyladenine modification Phase separation STYK1 |
| url | http://www.sciencedirect.com/science/article/pii/S2001037022004020 |
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