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Secondary structure prediction for RNA sequences including N6-methyladenosine

Author

Listed:
  • Elzbieta Kierzek

    (Institute of Bioorganic Chemistry Polish Academy of Sciences)

  • Xiaoju Zhang

    (University of Rochester)

  • Richard M. Watson

    (University of Rochester)

  • Scott D. Kennedy

    (University of Rochester)

  • Marta Szabat

    (Institute of Bioorganic Chemistry Polish Academy of Sciences)

  • Ryszard Kierzek

    (Institute of Bioorganic Chemistry Polish Academy of Sciences)

  • David H. Mathews

    (University of Rochester)

Abstract

There is increasing interest in the roles of covalently modified nucleotides in RNA. There has been, however, an inability to account for modifications in secondary structure prediction because of a lack of software and thermodynamic parameters. We report the solution for these issues for N6-methyladenosine (m6A), allowing secondary structure prediction for an alphabet of A, C, G, U, and m6A. The RNAstructure software now works with user-defined nucleotide alphabets of any size. We also report a set of nearest neighbor parameters for helices and loops containing m6A, using experiments. Interestingly, N6-methylation decreases folding stability for adenosines in the middle of a helix, has little effect on folding stability for adenosines at the ends of helices, and increases folding stability for unpaired adenosines stacked on a helix. We demonstrate predictions for an N6-methylation-activated protein recognition site from MALAT1 and human transcriptome-wide effects of N6-methylation on the probability of adenosine being buried in a helix.

Suggested Citation

  • Elzbieta Kierzek & Xiaoju Zhang & Richard M. Watson & Scott D. Kennedy & Marta Szabat & Ryszard Kierzek & David H. Mathews, 2022. "Secondary structure prediction for RNA sequences including N6-methyladenosine," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-28817-4
    DOI: 10.1038/s41467-022-28817-4
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    References listed on IDEAS

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    1. Nian Liu & Qing Dai & Guanqun Zheng & Chuan He & Marc Parisien & Tao Pan, 2015. "N6-methyladenosine-dependent RNA structural switches regulate RNA–protein interactions," Nature, Nature, vol. 518(7540), pages 560-564, February.
    2. Yue Wan & Kun Qu & Qiangfeng Cliff Zhang & Ryan A. Flynn & Ohad Manor & Zhengqing Ouyang & Jiajing Zhang & Robert C. Spitale & Michael P. Snyder & Eran Segal & Howard Y. Chang, 2014. "Landscape and variation of RNA secondary structure across the human transcriptome," Nature, Nature, vol. 505(7485), pages 706-709, January.
    3. Bei Liu & Dawn K. Merriman & Seung H. Choi & Maria A. Schumacher & Raphael Plangger & Christoph Kreutz & Stacy M. Horner & Kate D. Meyer & Hashim M. Al-Hashimi, 2018. "A potentially abundant junctional RNA motif stabilized by m6A and Mg2+," Nature Communications, Nature, vol. 9(1), pages 1-10, December.
    4. Thomas M. Carlile & Maria F. Rojas-Duran & Boris Zinshteyn & Hakyung Shin & Kristen M. Bartoli & Wendy V. Gilbert, 2014. "Pseudouridine profiling reveals regulated mRNA pseudouridylation in yeast and human cells," Nature, Nature, vol. 515(7525), pages 143-146, November.
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