A role for the C. elegans Argonaute protein CSR-1 in small nuclear RNA 3' processing.
PLoS Genet
; 20(5): e1011284, 2024 May.
Article
in En
| MEDLINE
| ID: mdl-38743783
ABSTRACT
The Integrator is a multi-subunit protein complex that catalyzes the maturation of snRNA transcripts via 3' cleavage, a step required for snRNA incorporation with snRNP for spliceosome biogenesis. Here we developed a GFP based in vivo snRNA misprocessing reporter as a readout of Integrator function and performed a genome-wide RNAi screen for Integrator regulators. We found that loss of the Argonaute encoding csr-1 gene resulted in widespread 3' misprocessing of snRNA transcripts that is accompanied by a significant increase in alternative splicing. Loss of the csr-1 gene down-regulates the germline expression of Integrator subunits 4 and 6 and is accompanied by a reduced protein translation efficiency of multiple Integrator catalytic and non-catalytic subunits. Through isoform and motif mutant analysis, we determined that CSR-1's effect on snRNA processing is dependent on its catalytic slicer activity but does not involve the CSR-1a isoform. Moreover, mRNA-sequencing revealed high similarity in the transcriptome profile between csr-1 and Integrator subunit knockdown via RNAi. Together, our findings reveal CSR-1 as a new regulator of the Integrator complex and implicate a novel role of this Argonaute protein in snRNA 3' processing.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
RNA, Small Nuclear
/
Caenorhabditis elegans
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Caenorhabditis elegans Proteins
/
Argonaute Proteins
Limits:
Animals
Language:
En
Journal:
PLoS Genet
/
PloS genet
/
PloS genetics
Journal subject:
GENETICA
Year:
2024
Document type:
Article
Affiliation country:
Canadá
Country of publication:
Estados Unidos