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Mettl3-dependent m6A modification attenuates the brain stress response in Drosophila

Author

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  • Alexandra E. Perlegos

    (University of Pennsylvania)

  • Emily J. Shields

    (University of Pennsylvania
    University of Pennsylvania Perelman School of Medicine
    University of Freiburg)

  • Hui Shen

    (University of Pennsylvania)

  • Kathy Fange Liu

    (University of Pennsylvania
    University of Pennsylvania)

  • Nancy M. Bonini

    (University of Pennsylvania
    University of Pennsylvania)

Abstract

N6-methyladenosine (m6A), the most prevalent internal modification on eukaryotic mRNA, plays an essential role in various stress responses. The brain is uniquely vulnerable to cellular stress, thus defining how m6A sculpts the brain’s susceptibility may provide insight to brain aging and disease-related stress. Here we investigate the impact of m6A mRNA methylation in the adult Drosophila brain with stress. We show that m6A is enriched in the adult brain and increases with heat stress. Through m6A-immunoprecipitation sequencing, we show 5′UTR Mettl3-dependent m6A is enriched in transcripts of neuronal processes and signaling pathways that increase upon stress. Mettl3 knockdown results in increased levels of m6A targets and confers resilience to stress. We find loss of Mettl3 results in decreased levels of nuclear m6A reader Ythdc1, and knockdown of Ythdc1 also leads to stress resilience. Overall, our data suggest that m6A modification in Drosophila dampens the brain’s biological response to stress.

Suggested Citation

  • Alexandra E. Perlegos & Emily J. Shields & Hui Shen & Kathy Fange Liu & Nancy M. Bonini, 2022. "Mettl3-dependent m6A modification attenuates the brain stress response in Drosophila," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-33085-3
    DOI: 10.1038/s41467-022-33085-3
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    References listed on IDEAS

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    1. Lijuan Kan & Stanislav Ott & Brian Joseph & Eun Sil Park & Wei Dai & Ralph E. Kleiner & Adam Claridge-Chang & Eric C. Lai, 2021. "A neural m6A/Ythdf pathway is required for learning and memory in Drosophila," Nature Communications, Nature, vol. 12(1), pages 1-18, December.
    2. Yang Xiang & Benoit Laurent & Chih-Hung Hsu & Sigrid Nachtergaele & Zhike Lu & Wanqiang Sheng & Chuanyun Xu & Hao Chen & Jian Ouyang & Siqing Wang & Dominic Ling & Pang-Hung Hsu & Lee Zou & Ashwini Ja, 2017. "Correction: Corrigendum: RNA m6A methylation regulates the ultraviolet-induced DNA damage response," Nature, Nature, vol. 552(7685), pages 430-430, December.
    3. Michael Lawrence & Wolfgang Huber & Hervé Pagès & Patrick Aboyoun & Marc Carlson & Robert Gentleman & Martin T Morgan & Vincent J Carey, 2013. "Software for Computing and Annotating Genomic Ranges," PLOS Computational Biology, Public Library of Science, vol. 9(8), pages 1-10, August.
    4. Jason R. Kennerdell & Nan Liu & Nancy M. Bonini, 2018. "MiR-34 inhibits polycomb repressive complex 2 to modulate chaperone expression and promote healthy brain aging," Nature Communications, Nature, vol. 9(1), pages 1-13, December.
    5. Yang Xiang & Benoit Laurent & Chih-Hung Hsu & Sigrid Nachtergaele & Zhike Lu & Wanqiang Sheng & Chuanyun Xu & Hao Chen & Jian Ouyang & Siqing Wang & Dominic Ling & Pang-Hung Hsu & Lee Zou & Ashwini Ja, 2017. "RNA m6A methylation regulates the ultraviolet-induced DNA damage response," Nature, Nature, vol. 543(7646), pages 573-576, March.
    6. Kazuo Emoto & Jay Z. Parrish & Lily Yeh Jan & Yuh-Nung Jan, 2006. "The tumour suppressor Hippo acts with the NDR kinases in dendritic tiling and maintenance," Nature, Nature, vol. 443(7108), pages 210-213, September.
    7. Jun Zhou & Ji Wan & Xiangwei Gao & Xingqian Zhang & Samie R. Jaffrey & Shu-Bing Qian, 2015. "Dynamic m6A mRNA methylation directs translational control of heat shock response," Nature, Nature, vol. 526(7574), pages 591-594, October.
    8. Xiao Wang & Zhike Lu & Adrian Gomez & Gary C. Hon & Yanan Yue & Dali Han & Ye Fu & Marc Parisien & Qing Dai & Guifang Jia & Bing Ren & Tao Pan & Chuan He, 2014. "N6-methyladenosine-dependent regulation of messenger RNA stability," Nature, Nature, vol. 505(7481), pages 117-120, January.
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