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Global identification of functional microRNA-mRNA interactions in Drosophila

Author

Listed:
  • Hans-Hermann Wessels

    (Max-Delbrück-Center for Molecular Medicine
    Humboldt University
    New York Genome Center)

  • Svetlana Lebedeva

    (Max-Delbrück-Center for Molecular Medicine)

  • Antje Hirsekorn

    (Max-Delbrück-Center for Molecular Medicine)

  • Ricardo Wurmus

    (Max-Delbrück-Center for Molecular Medicine)

  • Altuna Akalin

    (Max-Delbrück-Center for Molecular Medicine)

  • Neelanjan Mukherjee

    (Max-Delbrück-Center for Molecular Medicine
    University of Colorado School of Medicine)

  • Uwe Ohler

    (Max-Delbrück-Center for Molecular Medicine
    Humboldt University)

Abstract

MicroRNAs (miRNAs) are key mediators of post-transcriptional gene expression silencing. So far, no comprehensive experimental annotation of functional miRNA target sites exists in Drosophila. Here, we generated a transcriptome-wide in vivo map of miRNA-mRNA interactions in Drosophila melanogaster, making use of single nucleotide resolution in Argonaute1 (AGO1) crosslinking and immunoprecipitation (CLIP) data. Absolute quantification of cellular miRNA levels presents the miRNA pool in Drosophila cell lines to be more diverse than previously reported. Benchmarking two CLIP approaches, we identify a similar predictive potential to unambiguously assign thousands of miRNA-mRNA pairs from AGO1 interaction data at unprecedented depth, achieving higher signal-to-noise ratios than with computational methods alone. Quantitative RNA-seq and sub-codon resolution ribosomal footprinting data upon AGO1 depletion enabled the determination of miRNA-mediated effects on target expression and translation. We thus provide the first comprehensive resource of miRNA target sites and their quantitative functional impact in Drosophila.

Suggested Citation

  • Hans-Hermann Wessels & Svetlana Lebedeva & Antje Hirsekorn & Ricardo Wurmus & Altuna Akalin & Neelanjan Mukherjee & Uwe Ohler, 2019. "Global identification of functional microRNA-mRNA interactions in Drosophila," Nature Communications, Nature, vol. 10(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-09586-z
    DOI: 10.1038/s41467-019-09586-z
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    Cited by:

    1. Peike Sheng & Lu Li & Tianqi Li & Yuzhi Wang & Nicholas M. Hiers & Jennifer S. Mejia & Jossie S. Sanchez & Lei Zhou & Mingyi Xie, 2023. "Screening of Drosophila microRNA-degradation sequences reveals Argonaute1 mRNA’s role in regulating miR-999," Nature Communications, Nature, vol. 14(1), pages 1-14, December.

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