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| Status |
Public on Jun 03, 2021 |
| Title |
Cyclic dinucleotide stimulation of Nematostella vectensis |
| Organism |
Nematostella vectensis |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
In mammals, the cGAS-cGAMP-STING pathway is crucial for sensing viral infection and initiating an anti-viral type I interferon response. cGAS and STING are highly conserved genes that originated in bacteria and are present in most animals. By contrast, interferons only emerged in vertebrates; thus, the function of STING in invertebrates is unclear. Here, we use the STING ligand 2'3'-cGAMP to activate immune responses in a model cnidarian invertebrate, the starlet sea anemone Nematostella vectensis. Using RNA-Seq, we found that 2'3'-cGAMP induces robust transcription of both anti-viral and anti-bacterial genes, including the conserved transcription factor NF-κB. Knockdown experiments identified a role for NF-κB in specifically inducing anti-bacterial genes downstream of 2'3'-cGAMP, and some of these genes were also found to be induced during Pseudomonas aeruginosa infection. Furthermore, we characterized the protein product of one of the putative anti-bacterial genes, the N. vectensis homolog of Dae4, and found that it has conserved anti-bacterial activity. This work describes an unexpected role of a cGAMP sensing pathway in anti-bacterial immunity and suggests that a broad transcriptional response is an evolutionarily ancestral output of 2'3'-cGAMP signaling in animals.
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| Overall design |
Examine the response of N. vectensis polyps with cyclic dinucleotides (untreated, c-di-AMP, c-di-GMP, 2'3'-cGAMP, 3'3'-cGAMP). To determine factors required for the response to 2'3'-cGAMP, microinjected N. vectensis embryos with shRNAs targeting GFP (control), nvSTING, nvSTAT, and nvNF-kB and treated with 2'3'-cGAMP.
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| Contributor(s) |
Margolis S |
| Citation(s) |
34903650 |
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| Submission date |
Jun 02, 2021 |
| Last update date |
Dec 15, 2021 |
| Contact name |
Shally Rebecca Margolis |
| Organization name |
UC Berkeley
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| Department |
Molecular and Cell Biology
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| Lab |
Russell Vance
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| Street address |
415 Life Sciences
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| City |
Berkeley |
| State/province |
CA |
| ZIP/Postal code |
94720 |
| Country |
USA |
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| Platforms (2) |
| GPL29226 |
Illumina NovaSeq 6000 (Nematostella vectensis) |
| GPL29855 |
Illumina HiSeq 4000 (Nematostella vectensis) |
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| Samples (33)
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| GSM5352323 |
2'3'-cGAMP polyp 1 |
| GSM5352324 |
3'3'-cGAMP polyp 1 |
| GSM5352325 |
untreated polyp 2 |
| GSM5352326 |
c-di-AMP polyp 2 |
| GSM5352327 |
c-di-GMP polyp 2 |
| GSM5352328 |
2'3'-cGAMP polyp 2 |
| GSM5352329 |
3'3'-cGAMP polyp 2 |
| GSM5352330 |
GFP shRNA, 2'3'-cGAMP 1 |
| GSM5352331 |
NFkB shRNA 1, 2'3'-cGAMP 1 |
| GSM5352332 |
STAT shRNA 1, 2'3'-cGAMP 1 |
| GSM5352333 |
NFkB shRNA 2, 2'3'-cGAMP 1 |
| GSM5352334 |
STAT shRNA 2, 2'3'-cGAMP 1 |
| GSM5352335 |
GFP shRNA, 2'3'-cGAMP 2 |
| GSM5352336 |
NFkB shRNA 2, 2'3'-cGAMP 2 |
| GSM5352337 |
STAT shRNA 2, 2'3'-cGAMP 2 |
| GSM5352338 |
STAT shRNA 1, 2'3'-cGAMP 2 |
| GSM5352339 |
NFkB shRNA 1, 2'3'-cGAMP 2 |
| GSM5352340 |
GFP shRNA, 2'3'-cGAMP 3 |
| GSM5352341 |
GFP shRNA, untreated 1 |
| GSM5352342 |
GFP shRNA, 2'3'-cGAMP 4 |
| GSM5352343 |
STING shRNA 1, untreated 1 |
| GSM5352344 |
STING shRNA 1, 2'3'-cGAMP 1 |
| GSM5352345 |
STING shRNA 2, untreated 1 |
| GSM5352346 |
STING shRNA 2, 2'3'-cGAMP 1 |
| GSM5352347 |
GFP shRNA, untreated 2 |
| GSM5352348 |
GFP shRNA, 2'3'-cGAMP 5 |
| GSM5352349 |
STING shRNA 1, untreated 2 |
| GSM5352350 |
STING shRNA 1, 2'3'-cGAMP 2 |
| GSM5352351 |
STING shRNA 2, untreated 2 |
| GSM5352352 |
STING shRNA 2, 2'3'-cGAMP 2 |
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| Relations |
| BioProject |
PRJNA734503 |
| SRA |
SRP322326 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE175984_knockdowns_normalized_counts.txt.gz |
1.3 Mb |
(ftp)(http) |
TXT |
| GSE175984_nvSTINGexp_normalized_counts.txt.gz |
1.5 Mb |
(ftp)(http) |
TXT |
| GSE175984_polyps_normalized_counts.txt.gz |
954.4 Kb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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