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Optimized photochemistry enables efficient analysis of dynamic RNA structuromes and interactomes in genetic and infectious diseases

Author

Listed:
  • Minjie Zhang

    (University of Southern California)

  • Kongpan Li

    (University of Southern California)

  • Jianhui Bai

    (University of Southern California)

  • Willem A. Velema

    (Radboud University Nijmegen)

  • Chengqing Yu

    (University of Southern California)

  • Ryan van Damme

    (University of Southern California)

  • Wilson H. Lee

    (University of Southern California)

  • Maia L. Corpuz

    (University of Southern California)

  • Jian-Fu Chen

    (University of Southern California)

  • Zhipeng Lu

    (University of Southern California)

Abstract

Direct determination of RNA structures and interactions in living cells is critical for understanding their functions in normal physiology and disease states. Here, we present PARIS2, a dramatically improved method for RNA duplex determination in vivo with >4000-fold higher efficiency than previous methods. PARIS2 captures ribosome binding sites on mRNAs, reporting translation status on a transcriptome scale. Applying PARIS2 to the U8 snoRNA mutated in the neurological disorder LCC, we discover a network of dynamic RNA structures and interactions which are destabilized by patient mutations. We report the first whole genome structure of enterovirus D68, an RNA virus that causes polio-like symptoms, revealing highly dynamic conformations altered by antiviral drugs and different pathogenic strains. We also discover a replication-associated asymmetry on the (+) and (−) strands of the viral genome. This study establishes a powerful technology for efficient interrogation of the RNA structurome and interactome in human diseases.

Suggested Citation

  • Minjie Zhang & Kongpan Li & Jianhui Bai & Willem A. Velema & Chengqing Yu & Ryan van Damme & Wilson H. Lee & Maia L. Corpuz & Jian-Fu Chen & Zhipeng Lu, 2021. "Optimized photochemistry enables efficient analysis of dynamic RNA structuromes and interactomes in genetic and infectious diseases," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-22552-y
    DOI: 10.1038/s41467-021-22552-y
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    Cited by:

    1. Harshita Sharma & Matthew N. Z. Valentine & Naoko Toki & Hiromi Nishiyori Sueki & Stefano Gustincich & Hazuki Takahashi & Piero Carninci, 2024. "Decryption of sequence, structure, and functional features of SINE repeat elements in SINEUP non-coding RNA-mediated post-transcriptional gene regulation," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    2. Ryan Damme & Kongpan Li & Minjie Zhang & Jianhui Bai & Wilson H. Lee & Joseph D. Yesselman & Zhipeng Lu & Willem A. Velema, 2022. "Chemical reversible crosslinking enables measurement of RNA 3D distances and alternative conformations in cells," Nature Communications, Nature, vol. 13(1), pages 1-13, December.

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