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Interdependence of Pasha and Drosha for localization and function of the Microprocessor in C. elegans

Author

Listed:
  • Thiago L. Knittel

    (Colorado State University)

  • Brooke E. Montgomery

    (Colorado State University)

  • Kailee J. Reed

    (Colorado State University
    Colorado State University)

  • Madeleine C. Chong

    (Colorado State University)

  • Ida J. Isolehto

    (Institute of Molecular Biology
    Epigenetics and Genome Stability)

  • Erin R. Cafferty

    (Colorado State University)

  • Margaret J. Smith

    (Colorado State University)

  • Reese A. Sprister

    (Colorado State University)

  • Colin N. Magelky

    (Colorado State University)

  • Hataichanok Scherman

    (Colorado State University)

  • René F. Ketting

    (Institute of Molecular Biology
    Johannes Gutenberg University)

  • Taiowa A. Montgomery

    (Colorado State University
    Colorado State University)

Abstract

Primary microRNA (pri-miRNA) transcripts are processed by the Microprocessor, containing the ribonuclease Drosha and its RNA-binding partner DGCR8/Pasha. In a forward genetic screen utilizing a fluorescence-based sensor that monitors pri-miRNA processing in live Caenorhabditis elegans, we identify a mutation in the conserved G179 residue adjacent to the namesake W180 of Pasha’s WW domain that disrupts pri-miRNA processing. We show that both the G179 and W180 residues are required for Pasha dimerization and Microprocessor assembly. The WW domain also facilitates nuclear localization of Pasha, likely through its role in Microprocessor assembly, which in turn promotes nuclear enrichment of Drosha. Furthermore, depletion of Pasha mislocalizes Drosha to the cytoplasm, and vice versa, while deletion of Pasha’s N-terminus causes both proteins to accumulate in nucleoli. Our results reveal a mutual dependency between Pasha and Drosha for their localization in C. elegans and highlight the role of Pasha’s WW domain in maintaining Microprocessor integrity.

Suggested Citation

  • Thiago L. Knittel & Brooke E. Montgomery & Kailee J. Reed & Madeleine C. Chong & Ida J. Isolehto & Erin R. Cafferty & Margaret J. Smith & Reese A. Sprister & Colin N. Magelky & Hataichanok Scherman & , 2025. "Interdependence of Pasha and Drosha for localization and function of the Microprocessor in C. elegans," Nature Communications, Nature, vol. 16(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-60721-5
    DOI: 10.1038/s41467-025-60721-5
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