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Expanded palette of RNA base editors for comprehensive RBP-RNA interactome studies

Author

Listed:
  • Hugo C. Medina-Munoz

    (University of California San Diego
    University of California San Diego
    University of California San Diego)

  • Eric Kofman

    (University of California San Diego
    University of California San Diego
    University of California San Diego
    University of California San Diego)

  • Pratibha Jagannatha

    (University of California San Diego
    University of California San Diego
    University of California San Diego
    University of California San Diego)

  • Evan A. Boyle

    (University of California San Diego
    University of California San Diego
    University of California San Diego)

  • Tao Yu

    (University of California San Diego
    University of California San Diego
    University of California San Diego)

  • Krysten L. Jones

    (University of California San Diego
    University of California San Diego
    University of California San Diego)

  • Jasmine R. Mueller

    (University of California San Diego
    University of California San Diego
    University of California San Diego)

  • Grace D. Lykins

    (University of California San Diego
    University of California San Diego
    University of California San Diego)

  • Andrew T. Doudna

    (University of California San Diego
    University of California San Diego
    University of California San Diego)

  • Samuel S. Park

    (University of California San Diego
    University of California San Diego
    University of California San Diego)

  • Steven M. Blue

    (University of California San Diego
    University of California San Diego
    University of California San Diego)

  • Brodie L. Ranzau

    (University of California San Diego)

  • Rahul M. Kohli

    (University of Pennsylvania
    University of Pennsylvania)

  • Alexis C. Komor

    (University of California San Diego)

  • Gene W. Yeo

    (University of California San Diego
    University of California San Diego
    University of California San Diego
    University of California San Diego)

Abstract

RNA binding proteins (RBPs) are key regulators of RNA processing and cellular function. Technologies to discover RNA targets of RBPs such as TRIBE (targets of RNA binding proteins identified by editing) and STAMP (surveying targets by APOBEC1 mediated profiling) utilize fusions of RNA base-editors (rBEs) to RBPs to circumvent the limitations of immunoprecipitation (CLIP)-based methods that require enzymatic digestion and large amounts of input material. To broaden the repertoire of rBEs suitable for editing-based RBP-RNA interaction studies, we have devised experimental and computational assays in a framework called PRINTER (protein-RNA interaction-based triaging of enzymes that edit RNA) to assess over thirty A-to-I and C-to-U rBEs, allowing us to identify rBEs that expand the characterization of binding patterns for both sequence-specific and broad-binding RBPs. We also propose specific rBEs suitable for dual-RBP applications. We show that the choice between single or multiple rBEs to fuse with a given RBP or pair of RBPs hinges on the editing biases of the rBEs and the binding preferences of the RBPs themselves. We believe our study streamlines and enhances the selection of rBEs for the next generation of RBP-RNA target discovery.

Suggested Citation

  • Hugo C. Medina-Munoz & Eric Kofman & Pratibha Jagannatha & Evan A. Boyle & Tao Yu & Krysten L. Jones & Jasmine R. Mueller & Grace D. Lykins & Andrew T. Doudna & Samuel S. Park & Steven M. Blue & Brodi, 2024. "Expanded palette of RNA base editors for comprehensive RBP-RNA interactome studies," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-45009-4
    DOI: 10.1038/s41467-024-45009-4
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    References listed on IDEAS

    as
    1. Hongzhi Zeng & Qichen Yuan & Fei Peng & Dacheng Ma & Ananya Lingineni & Kelly Chee & Peretz Gilberd & Emmanuel C. Osikpa & Zheng Sun & Xue Gao, 2023. "A split and inducible adenine base editor for precise in vivo base editing," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    2. Julie M. Eggington & Tom Greene & Brenda L. Bass, 2011. "Predicting sites of ADAR editing in double-stranded RNA," Nature Communications, Nature, vol. 2(1), pages 1-9, September.
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    Cited by:

    1. Phillipp Torkler & Marina Sauer & Uwe Schwartz & Selim Corbacioglu & Gunhild Sommer & Tilman Heise, 2024. "LoDEI: a robust and sensitive tool to detect transcriptome-wide differential A-to-I editing in RNA-seq data," Nature Communications, Nature, vol. 15(1), pages 1-11, December.
    2. Qishan Liang & Tao Yu & Eric Kofman & Pratibha Jagannatha & Kevin Rhine & Brian A. Yee & Kevin D. Corbett & Gene W. Yeo, 2024. "High-sensitivity in situ capture of endogenous RNA-protein interactions in fixed cells and primary tissues," Nature Communications, Nature, vol. 15(1), pages 1-16, December.

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