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| Status |
Public on Jan 26, 2024 |
| Title |
The helicase domain of human Dicer prevents RNAi-independent activation of antiviral and inflammatory pathways |
| Organisms |
Homo sapiens; Sindbis virus |
| Experiment type |
Other
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| Summary |
In mammalian somatic cells, the relative contribution of RNAi and the type I interferon response during viral infection is unclear. The apparent inefficiency of antiviral RNAi might be due to self-limiting properties and mitigating co-factors of the key enzyme Dicer. In particular, the helicase domain of human Dicer appears to be an important restriction factor of its activity. Here, we study the involvement of several helicase-truncated mutants of human Dicer in the antiviral response. All deletion mutants display a PKR-dependent antiviral phenotype against certain viruses, and one of them, Dicer N1, acts in a completely RNAi-independent manner. Transcriptomic analyses show that many genes from the interferon and inflammatory response pathways are upregulated in Dicer N1-expressing cells. We show that some of these genes are controlled by NF-kB and that blocking this pathway abrogates the antiviral phenotype of Dicer N1. Our findings highlight the crosstalk between Dicer, PKR, and the NF-kB pathway, and suggest that human Dicer may have repurposed its helicase domain to prevent basal activation of antiviral and inflammatory pathways.
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| Overall design |
NoDice FHA:DICER WT #4 or N1 #6 cells were infected with a modified version of Sindbis virus expressing GFP at an MOI of 0.02 for 24 h. To enrich in small RNAs, Argonautes-IPs (AGO-IP) were done using the TNRC6B peptide in Sindbis infected cells followed by small RNA extraction. In parallel, a control IP (CTL IP) was performed. The experiment was done in 3 biological replicates. RNAs coming from AGO IP for the 3 replicates or from the CTL IP for one replicate in Sindbis infected samples (MOI of 0.02 at 24 hpi) were analyzed for both cell lines. Small RNA sequencing aimed to investigate an RNAi pattern for the Dicer isoform in the context of Sindbis virus infection.
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| Contributor(s) |
Baldaccini M, Gaucherand L, Chane-Woon-Ming B, Messmer M, Gucciardi F, Pfeffer S |
| Citation(s) |
38287188 |
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| Submission date |
Aug 29, 2023 |
| Last update date |
Mar 13, 2024 |
| Contact name |
Sébastien Pfeffer |
| Organization name |
CNRS - Institut de Biologie Moléculaire et Cellulaire (IBMC)
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| Department |
UPR 9002 - Architecture et Réactivité de l'ARN
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| Lab |
RNA regulation in viral infections
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| Street address |
2 allée Konrad Roentgen
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| City |
Strasbourg |
| ZIP/Postal code |
67084 |
| Country |
France |
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| Platforms (1) |
| GPL33716 |
Illumina HiSeq 4000 (Homo sapiens; Sindbis virus) |
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| Samples (8)
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| GSM7743920 |
AGO IP, Dicer WT, SINV-GFP MOI 0.02 24 hpi, rep1 |
| GSM7743921 |
AGO IP, Dicer WT, SINV-GFP MOI 0.02 24 hpi, rep2 |
| GSM7743922 |
AGO IP, Dicer WT, SINV-GFP MOI 0.02 24 hpi, rep3 |
| GSM7743923 |
AGO IP, Dicer N1, SINV-GFP MOI 0.02 24 hpi, rep1 |
| GSM7743924 |
AGO IP, Dicer N1, SINV-GFP MOI 0.02 24 hpi, rep2 |
| GSM7743925 |
AGO IP, Dicer N1, SINV-GFP MOI 0.02 24 hpi, rep3 |
| GSM7743926 |
CTL IP, Dicer WT, SINV-GFP MOI 0.02 24 hpi, rep1 |
| GSM7743927 |
CTL IP, Dicer N1, SINV-GFP, MOI 0.02 24 hpi, rep1 |
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| This SubSeries is part of SuperSeries: |
| GSE241798 |
The helicase domain of human Dicer prevents RNAi-independent activation of antiviral and inflammatory pathways |
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| Relations |
| BioProject |
PRJNA1010106 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE241797_RAW.tar |
14.6 Mb |
(http)(custom) |
TAR (of BW, TXT) |
| GSE241797_hsa-matmir_deseq2_normcounts.txt.gz |
40.0 Kb |
(ftp)(http) |
TXT |
| GSE241797_hsa-matmir_rawcounts.txt.gz |
22.2 Kb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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