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

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, René F. Ketting and Taiowa A. Montgomery ()
Additional contact information
Thiago L. Knittel: Colorado State University
Brooke E. Montgomery: Colorado State University
Kailee J. Reed: Colorado State University
Madeleine C. Chong: Colorado State University
Ida J. Isolehto: Institute of Molecular Biology
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
Taiowa A. Montgomery: Colorado State University

Nature Communications, 2025, vol. 16, issue 1, 1-17

Abstract: 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.

Date: 2025
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-025-60721-5 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-60721-5

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-025-60721-5

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().