Protein arginine methyltransferase 3 (PRMT3), a type I arginine methyltransferase is localized predominantly in the cytoplasm and regulates different cellular functions. Nevertheless, PRMT3 also exhibits regulatory functions in the nucleus by interacting with the liver X receptor alpha (LXRα) and catalyzes asymmetric dimethylation modifications at arginine 3 of histone 4 (H4R3me2a). However, very little is known about the regulation of the versatile global regulator PRMT3 and how PRMT3 is translocated to the nucleus. In this study, we identified ZNF200, a hitherto uncharacterized protein, as a potential binding partner of PRMT3 through yeast two-hybrid screening. We confirmed the interaction of PRMT3 with ZNF200 using immunoprecipitation and in vitro pull-down experiments. GST pull-down experiments and molecular docking studies revealed that the N-terminal zinc finger domain of PRMT3 binds to the C-terminal zinc finger regions of ZNF200. Furthermore, the evolutionary conservation of the Znf domain of PRMT3 correlates with the emergence of ZNF200 in mammals. We found that ZNF200 stabilizes PRMT3 by inhibiting its proteasomal degradation. ZNF200, a nuclear-predominant protein, promotes the nuclear translocation of PRMT3, leading to the global increase of H4R3me2a modifications. These findings imply that ZNF200 is a critical regulator of the steady-state levels and nuclear and epigenetic functions of PRMT3.
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The cover of this issue of the Biochemical Journal features confocal imaging of internalisation of the APJR-EGFP receptor transiently expressed in HEK293T cells, read more in "Divergent roles of DRY and NPxxY motifs in selective activation of downstream signalling by the apelin receptor" by Aradhyam and colleagues on pages 1707–1722.
Research Article|
November 21 2024
The uncharacterized protein ZNF200 interacts with PRMT3 and aids its stability and nuclear translocation
Somlee Gupta;
Somlee Gupta
Conceptualization, Validation, Investigation, Visualization, Methodology, Writing - original draft
1Department of Biotechnology, Pondicherry University, Puducherry 605 014, India
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Mamta Verma;
Mamta Verma
Validation, Investigation, Methodology
1Department of Biotechnology, Pondicherry University, Puducherry 605 014, India
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Rajashekar Varma Kadumuri;
Rajashekar Varma Kadumuri
Validation, Investigation, Visualization, Methodology
2Department of Biology, Indian Institute of Science Education and Research (IISER) Tirupati, Tirupati 517 507, Andhra Pradesh, India
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Namita Chutani;
Namita Chutani
Validation, Investigation, Methodology
2Department of Biology, Indian Institute of Science Education and Research (IISER) Tirupati, Tirupati 517 507, Andhra Pradesh, India
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Mohd. Imran K. Khan;
Mohd. Imran K. Khan
Validation, Investigation, Methodology
1Department of Biotechnology, Pondicherry University, Puducherry 605 014, India
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Sreenivas Chavali;
Conceptualization, Formal analysis, Supervision, Funding acquisition, Visualization, Methodology, Writing - original draft, Project administration, Writing - review & editing
2Department of Biology, Indian Institute of Science Education and Research (IISER) Tirupati, Tirupati 517 507, Andhra Pradesh, India
Correspondence: Sreenivas Chavali ([email protected]) Arunkumar Dhayalan ([email protected])
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Arunkumar Dhayalan
Conceptualization, Formal analysis, Supervision, Funding acquisition, Visualization, Methodology, Writing - original draft, Project administration, Writing - review & editing
1Department of Biotechnology, Pondicherry University, Puducherry 605 014, India
Correspondence: Sreenivas Chavali ([email protected]) Arunkumar Dhayalan ([email protected])
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Publisher: Portland Press Ltd
Received:
August 21 2024
Revision Received:
November 06 2024
Accepted:
November 08 2024
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© 2024 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society
2024
Biochem J (2024) 481 (23): 1723–1740.
Article history
Received:
August 21 2024
Revision Received:
November 06 2024
Accepted:
November 08 2024
Citation
Somlee Gupta, Mamta Verma, Rajashekar Varma Kadumuri, Namita Chutani, Mohd. Imran K. Khan, Sreenivas Chavali, Arunkumar Dhayalan; The uncharacterized protein ZNF200 interacts with PRMT3 and aids its stability and nuclear translocation. Biochem J 4 December 2024; 481 (23): 1723–1740. doi: https://doi.org/10.1042/BCJ20240476
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