| RRC ID |
88026
|
| 著者 |
Knittel TL, Montgomery BE, Reed KJ, Chong MC, Isolehto IJ, Cafferty ER, Smith MJ, Sprister RA, Magelky CN, Scherman H, Ketting RF, Montgomery TA.
|
| タイトル |
Interdependence of Pasha and Drosha for localization and function of the Microprocessor in C. elegans.
|
| ジャーナル |
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.
|
| 巻・号 |
16(1)
|
| ページ |
5595
|
| 公開日 |
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
|
| リソース情報 |
| 線虫 |
tm2884 |
