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Differential analysis of RNA structure probing experiments at nucleotide resolution: uncovering regulatory functions of RNA structure

Author

Listed:
  • Bo Yu

    (Tsinghua University)

  • Pan Li

    (Tsinghua University
    Tsinghua University)

  • Qiangfeng Cliff Zhang

    (Tsinghua University
    Tsinghua University)

  • Lin Hou

    (Tsinghua University
    Tsinghua University)

Abstract

RNAs perform their function by forming specific structures, which can change across cellular conditions. Structure probing experiments combined with next generation sequencing technology have enabled transcriptome-wide analysis of RNA secondary structure in various cellular conditions. Differential analysis of structure probing data in different conditions can reveal the RNA structurally variable regions (SVRs), which is important for understanding RNA functions. Here, we propose DiffScan, a computational framework for normalization and differential analysis of structure probing data in high resolution. DiffScan preprocesses structure probing datasets to remove systematic bias, and then scans the transcripts to identify SVRs and adaptively determines their lengths and locations. The proposed approach is compatible with most structure probing platforms (e.g., icSHAPE, DMS-seq). When evaluated with simulated and benchmark datasets, DiffScan identifies structurally variable regions at nucleotide resolution, with substantial improvement in accuracy compared with existing SVR detection methods. Moreover, the improvement is robust when tested in multiple structure probing platforms. Application of DiffScan in a dataset of multi-subcellular RNA structurome and a subsequent motif enrichment analysis suggest potential links of RNA structural variation and mRNA abundance, possibly mediated by RNA binding proteins such as the serine/arginine rich splicing factors. This work provides an effective tool for differential analysis of RNA secondary structure, reinforcing the power of structure probing experiments in deciphering the dynamic RNA structurome.

Suggested Citation

  • Bo Yu & Pan Li & Qiangfeng Cliff Zhang & Lin Hou, 2022. "Differential analysis of RNA structure probing experiments at nucleotide resolution: uncovering regulatory functions of RNA structure," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-31875-3
    DOI: 10.1038/s41467-022-31875-3
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    1. Sidika Tapsin & Miao Sun & Yang Shen & Huibin Zhang & Xin Ni Lim & Teodorus Theo Susanto & Siwy Ling Yang & Gui Sheng Zeng & Jasmine Lee & Alexander Lezhava & Ee Lui Ang & Lian Hui Zhang & Yue Wang & , 2018. "Genome-wide identification of natural RNA aptamers in prokaryotes and eukaryotes," Nature Communications, Nature, vol. 9(1), pages 1-10, December.
    2. Robert C. Spitale & Ryan A. Flynn & Qiangfeng Cliff Zhang & Pete Crisalli & Byron Lee & Jong-Wha Jung & Hannes Y. Kuchelmeister & Pedro J. Batista & Eduardo A. Torre & Eric T. Kool & Howard Y. Chang, 2015. "Erratum: Structural imprints in vivo decode RNA regulatory mechanisms," Nature, Nature, vol. 527(7577), pages 264-264, November.
    3. 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.
    4. Hua Li & Sharon Aviran, 2018. "Publisher Correction: Statistical modeling of RNA structure profiling experiments enables parsimonious reconstruction of structure landscapes," Nature Communications, Nature, vol. 9(1), pages 1-1, December.
    5. Hua Li & Sharon Aviran, 2018. "Statistical modeling of RNA structure profiling experiments enables parsimonious reconstruction of structure landscapes," Nature Communications, Nature, vol. 9(1), pages 1-13, December.
    6. Robert C. Spitale & Ryan A. Flynn & Qiangfeng Cliff Zhang & Pete Crisalli & Byron Lee & Jong-Wha Jung & Hannes Y. Kuchelmeister & Pedro J. Batista & Eduardo A. Torre & Eric T. Kool & Howard Y. Chang, 2015. "Structural imprints in vivo decode RNA regulatory mechanisms," Nature, Nature, vol. 519(7544), pages 486-490, March.
    7. Silvi Rouskin & Meghan Zubradt & Stefan Washietl & Manolis Kellis & Jonathan S. Weissman, 2014. "Genome-wide probing of RNA structure reveals active unfolding of mRNA structures in vivo," Nature, Nature, vol. 505(7485), pages 701-705, January.
    8. Noemi Fernandez & Ross A. Cordiner & Robert S. Young & Nele Hug & Sara Macias & Javier F. Cáceres, 2017. "Genetic variation and RNA structure regulate microRNA biogenesis," Nature Communications, Nature, vol. 8(1), pages 1-12, August.
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