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Secondary structure RNA elements control the cleavage activity of DICER

Author

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  • Trung Duc Nguyen

    (The Hong Kong University of Science and Technology)

  • Tam Anh Trinh

    (The Hong Kong University of Science and Technology)

  • Sheng Bao

    (The Hong Kong University of Science and Technology)

  • Tuan Anh Nguyen

    (The Hong Kong University of Science and Technology)

Abstract

The accurate and efficient cleavage of shRNAs and pre-miRNAs by DICER is crucial for their gene-silencing activity. Here, we conduct high-throughput DICER cleavage assays for more than ~20,000 different shRNAs and show the comprehensive cleavage activities of DICER on these sequences. We discover a single-nucleotide bulge (22-bulge), which facilitates the cleavage activity of DICER on shRNAs and human pre-miRNAs. As a result, this 22-bulge enhances the gene-silencing activity of shRNAs and the accuracy of miRNA biogenesis. In addition, various single-nucleotide polymorphism-edited 22-bulges are found to govern the cleavage sites of DICER on pre-miRNAs and thereby control their functions. Finally, we identify the single cleavage of DICER and reveal its molecular mechanism. Our findings improve the understanding of the DICER cleavage mechanism, provide a foundation for the design of accurate and efficient shRNAs for gene-silencing, and indicate the function of bulges in regulating miRNA biogenesis.

Suggested Citation

  • Trung Duc Nguyen & Tam Anh Trinh & Sheng Bao & Tuan Anh Nguyen, 2022. "Secondary structure RNA elements control the cleavage activity of DICER," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-29822-3
    DOI: 10.1038/s41467-022-29822-3
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    References listed on IDEAS

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    1. Jeffrey Vedanayagam & Walid K. Chatila & Bülent Arman Aksoy & Sonali Majumdar & Anders Jacobsen Skanderup & Emek Demir & Nikolaus Schultz & Chris Sander & Eric C. Lai, 2019. "Cancer-associated mutations in DICER1 RNase IIIa and IIIb domains exert similar effects on miRNA biogenesis," Nature Communications, Nature, vol. 10(1), pages 1-14, December.
    2. Emily Bernstein & Amy A. Caudy & Scott M. Hammond & Gregory J. Hannon, 2001. "Role for a bidentate ribonuclease in the initiation step of RNA interference," Nature, Nature, vol. 409(6818), pages 363-366, January.
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