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Genome-wide probing of eukaryotic nascent RNA structure elucidates cotranscriptional folding and its antimutagenic effect

Author

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  • Gongwang Yu

    (Sun Yat-sen University
    Sun Yat-sen University)

  • Yao Liu

    (Sun Yat-sen University
    Sun Yat-sen University)

  • Zizhang Li

    (Sun Yat-sen University)

  • Shuyun Deng

    (Sun Yat-sen University)

  • Zhuoxing Wu

    (Sun Yat-sen University)

  • Xiaoyu Zhang

    (Sun Yat-sen University
    Sun Yat-sen University)

  • Wenbo Chen

    (Sun Yat-sen University)

  • Junnan Yang

    (Sun Yat-sen University)

  • Xiaoshu Chen

    (Sun Yat-sen University
    Sun Yat-sen University
    Sun Yat-sen University)

  • Jian-Rong Yang

    (Sun Yat-sen University
    Sun Yat-sen University
    Sun Yat-sen University)

Abstract

The transcriptional intermediates of RNAs fold into secondary structures with multiple regulatory roles, yet the details of such cotranscriptional RNA folding are largely unresolved in eukaryotes. Here, we present eSPET-seq (Structural Probing of Elongating Transcripts in eukaryotes), a method to assess the cotranscriptional RNA folding in Saccharomyces cerevisiae. Our study reveals pervasive structural transitions during cotranscriptional folding and overall structural similarities between nascent and mature RNAs. Furthermore, a combined analysis with genome-wide R-loop and mutation rate approximations provides quantitative evidence for the antimutator effect of nascent RNA folding through competitive inhibition of the R-loops, known to facilitate transcription-associated mutagenesis. Taken together, we present an experimental evaluation of cotranscriptional folding in eukaryotes and demonstrate the antimutator effect of nascent RNA folding. These results suggest genome-wide coupling between the processing and transmission of genetic information through RNA folding.

Suggested Citation

  • Gongwang Yu & Yao Liu & Zizhang Li & Shuyun Deng & Zhuoxing Wu & Xiaoyu Zhang & Wenbo Chen & Junnan Yang & Xiaoshu Chen & Jian-Rong Yang, 2023. "Genome-wide probing of eukaryotic nascent RNA structure elucidates cotranscriptional folding and its antimutagenic effect," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-41550-w
    DOI: 10.1038/s41467-023-41550-w
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