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Limited effects of m6A modification on mRNA partitioning into stress granules

Author

Listed:
  • Anthony Khong

    (University of Colorado
    Howard Hughes Medical Institute)

  • Tyler Matheny

    (University of Colorado
    University of Colorado Anschutz Medical Campus)

  • Thao Ngoc Huynh

    (University of Colorado)

  • Vincent Babl

    (University of Colorado)

  • Roy Parker

    (University of Colorado
    Howard Hughes Medical Institute)

Abstract

The presence of the m6A modification in mammalian mRNAs is proposed to promote mRNA recruitment to stress granules through the interaction with YTHDF proteins. We test this possibility by examining the accumulation of mRNAs in stress granules in both WT and ∆METTL3 mES cells, which are deficient in m6A modification. A critical observation is that all m6A modified mRNAs partition similarly into stress granules in both wild-type and m6A-deficient cells by single-molecule FISH. Moreover, multiple linear regression analysis indicates m6A modification explains only 6% of the variance in stress granule localization when controlled for length. Finally, the artificial tethering of 25 YTHDF proteins on reporter mRNAs leads to only a modest increase in mRNA partitioning to stress granules. Since most mammalian mRNAs have 4 or fewer m6A sites, and those sites are not fully modified, this argues m6A modifications are unlikely to play a significant role in recruiting mRNAs to stress granules. Taken together, these observations argue that m6A modifications play a minimal, if any, role in mRNA partitioning into stress granules.

Suggested Citation

  • Anthony Khong & Tyler Matheny & Thao Ngoc Huynh & Vincent Babl & Roy Parker, 2022. "Limited effects of m6A modification on mRNA partitioning into stress granules," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-31358-5
    DOI: 10.1038/s41467-022-31358-5
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    1. 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.
    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. "RNA m6A methylation regulates the ultraviolet-induced DNA damage response," Nature, Nature, vol. 543(7646), pages 573-576, March.
    3. Ryan J. Ries & Sara Zaccara & Pierre Klein & Anthony Olarerin-George & Sim Namkoong & Brian F. Pickering & Deepak P. Patil & Hojoong Kwak & Jun Hee Lee & Samie R. Jaffrey, 2019. "m6A enhances the phase separation potential of mRNA," Nature, Nature, vol. 571(7765), pages 424-428, July.
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    1. Cristina Leoni & Marian Bataclan & Taku Ito-Kureha & Vigo Heissmeyer & Silvia Monticelli, 2023. "The mRNA methyltransferase Mettl3 modulates cytokine mRNA stability and limits functional responses in mast cells," Nature Communications, Nature, vol. 14(1), pages 1-17, December.

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