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Predicting sites of ADAR editing in double-stranded RNA

Author

Listed:
  • Julie M. Eggington

    (University of Utah)

  • Tom Greene

    (University of Utah Health Sciences Center)

  • Brenda L. Bass

    (University of Utah)

Abstract

ADAR (adenosine deaminase that acts on RNA) editing enzymes target coding and noncoding double-stranded RNA (dsRNA) and are essential for neuronal function. Early studies showed that ADARs preferentially target adenosines with certain 5′ and 3′ neighbours. Here we use current Sanger sequencing protocols to perform a more accurate and quantitative analysis. We quantified editing sites in an ∼800-bp dsRNA after reaction with human ADAR1 or ADAR2, or their catalytic domains alone. These large data sets revealed that neighbour preferences are mostly dictated by the catalytic domain, but ADAR2's dsRNA-binding motifs contribute to 3′ neighbour preferences. For all proteins, the 5′ nearest neighbour was most influential, but adjacent bases also affected editing site choice. We developed algorithms to predict editing sites in dsRNA of any sequence, and provide a web-based application. The predictive power of the algorithm on fully base-paired dsRNA, compared with biological substrates containing mismatches, bulges and loops, elucidates structural contributions to editing specificity.

Suggested Citation

  • 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.
  • Handle: RePEc:nat:natcom:v:2:y:2011:i:1:d:10.1038_ncomms1324
    DOI: 10.1038/ncomms1324
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    Cited by:

    1. Suba Rajendren & Xiang Ye & William Dunker & Antiana Richardson & John Karijolich, 2023. "The cellular and KSHV A-to-I RNA editome in primary effusion lymphoma and its role in the viral lifecycle," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    2. Karthika Devi Kiran Kumar & Shubhangi Singh & Stella Maria Schmelzle & Paul Vogel & Carolin Fruhner & Alfred Hanswillemenke & Adrian Brun & Jacqueline Wettengel & Yvonne Füll & Lukas Funk & Valentin M, 2024. "An improved SNAP-ADAR tool enables efficient RNA base editing to interfere with post-translational protein modification," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    3. Orshay Gabay & Yoav Shoshan & Eli Kopel & Udi Ben-Zvi & Tomer D. Mann & Noam Bressler & Roni Cohen‐Fultheim & Amos A. Schaffer & Shalom Hillel Roth & Ziv Tzur & Erez Y. Levanon & Eli Eisenberg, 2022. "Landscape of adenosine-to-inosine RNA recoding across human tissues," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    4. 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.
    5. Marlon S. Zambrano-Mila & Monika Witzenberger & Zohar Rosenwasser & Anna Uzonyi & Ronit Nir & Shay Ben-Aroya & Erez Y. Levanon & Schraga Schwartz, 2023. "Dissecting the basis for differential substrate specificity of ADAR1 and ADAR2," Nature Communications, Nature, vol. 14(1), pages 1-14, December.

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