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RRC ID 88026
Author Knittel TL, Montgomery BE, Reed KJ, Chong MC, Isolehto IJ, Cafferty ER, Smith MJ, Sprister RA, Magelky CN, Scherman H, Ketting RF, Montgomery TA.
Title Interdependence of Pasha and Drosha for localization and function of the Microprocessor in C. elegans.
Journal Nat Commun
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.
Volume 16(1)
Pages 5595
Published 2025-7-1
DOI 10.1038/s41467-025-60721-5
PII 10.1038/s41467-025-60721-5
PMID 40595566
PMC PMC12219410
MeSH Animals Caenorhabditis elegans* / genetics Caenorhabditis elegans* / metabolism Caenorhabditis elegans Proteins* / chemistry Caenorhabditis elegans Proteins* / genetics Caenorhabditis elegans Proteins* / metabolism Cell Nucleus / metabolism MicroRNAs / genetics MicroRNAs / metabolism Mutation RNA Processing, Post-Transcriptional RNA-Binding Proteins* / genetics RNA-Binding Proteins* / metabolism Ribonuclease III* / genetics Ribonuclease III* / metabolism
Resource
C.elegans tm2884