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Functional analysis of the methyltransferase SMYD in the single-cell model organism Tetrahymena thermophila

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Abstract

Lysine methylation of histones and non-histones plays a pivotal role in diverse cellular processes. The SMYD (SET and MYND domain) family methyltransferases can methylate various histone and non-histone substrates in mammalian systems, implicated in HSP90 methylation, myofilament organization, cancer inhibition, and gene transcription regulation. To resolve controversies concerning SMYD’s substrates and functions, we studied SMYD1 (TTHERM_00578660), the only homologue of SMYD in the unicellular eukaryote Tetrahymena thermophila. We epitope-tagged SMYD1, and analyzed its localization and interactome. We also characterized ΔSMYD1 cells, focusing on the replication and transcription phenotype. Our results show that: (1) SMYD1 is present in both cytoplasm and transcriptionally active macronucleus and shuttles between cytoplasm and macronucleus, suggesting its potential association with both histone and non-histone substrates; (2) SMYD1 is involved in DNA replication and regulates transcription of metabolism-related genes; (3) HSP90 is a potential substrate for SMYD1 and it may regulate target selection of HSP90, leading to pleiotropic effects in both the cytoplasm and the nucleus.

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Data availability

RNA-seq datasets have been deposited to NCBI with accession number GEO: GSE138246.

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Acknowledgements

This work was supported by the Natural Science Foundation of Shandong Province (JQ201706 to SG), Fundamental Research Funds for the Central Universities (201841013 to SG), National Science Foundation [MCB 1411565 to YL], and National Institutes of Health Foundation [R01 GM087343 to YL]. XZ was supported by China Scholarship Council Scholarship for joint PhD students. Our thanks are given to Ms. Yuanyuan Wang (Laboratory of Protozoology, Ocean University of China), for helping with the preparation of Fig. 1.

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Authors and Affiliations

  1. Institute of Evolution and Marine Biodiversity, Ocean University of China, Qingdao, 266003, China

    Xiaolu Zhao, Yuan Li, Lili Duan, Xiao Chen, Weibo Song & Shan Gao

  2. Department of Pathology, University of Michigan, Ann Arbor, MI, 48109, USA

    Xiaolu Zhao, Fengbiao Mao, Mina Juma & Yifan Liu

  3. Laboratory for Marine Biology and Biotechnology, Qingdao National Laboratory for Marine Science and Technology, Qingdao, 266003, China

    Xiaolu Zhao, Yuan Li, Lili Duan, Weibo Song & Shan Gao

Authors
  1. Xiaolu Zhao
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  2. Yuan Li
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  3. Lili Duan
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  4. Xiao Chen
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  5. Fengbiao Mao
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  6. Mina Juma
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  7. Yifan Liu
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  8. Weibo Song
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  9. Shan Gao
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Contributions

SG, YFL and XLZ participated in study design. XLZ carried out most of the experiments. YL conducted the establishment of HSP90-Nflag/SMYD1-CHA-overexpression strain and LLD prepared the RNA-seq samples. XC and FBM conducted the bioinformatics analysis. Manuscript writing was conducted by XLZ with assistance from SG, YFL, WBS and MJ. All authors have read and approved the final manuscript.

Corresponding author

Correspondence to Shan Gao.

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This article does not contain any studies with human participants or animals performed by any of the authors.

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Edited by Jiamei Li.

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Zhao, X., Li, Y., Duan, L. et al. Functional analysis of the methyltransferase SMYD in the single-cell model organism Tetrahymena thermophila. Mar Life Sci Technol 2, 109–122 (2020). https://doi.org/10.1007/s42995-019-00025-y

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  • DOI: https://doi.org/10.1007/s42995-019-00025-y

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