WormCat: an online tool for annotation and visualization of Caenorhabditis elegans genome-scale data

Holdorf, Amy D.; Higgins, Daniel P.; Hart, Anne C.; Boag, Peter R.; Pazour, Gregory J.; Walhout, Albertha J.M.; Walker, Alec J.

doi:10.1101/844928

Cited by 38 publications

(86 citation statements)

References 18 publications

(25 reference statements)

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“…1C) (Amrit and Ghazi, 2017b). Analysis of this data through WormCat, a C. elegans bioinformatics platform that allows greater refinement of functional categories within enriched groups (Holdorf et al, 2020), substantiated these observations. Within the UP class, stress response, particularly pathogen response, was the second highest enriched category, and within the DOWN class, it was the most enriched one (Fig.…”

Section: Nhr-49 Widely Modulates the Expression Of Innate-immunity Genesmentioning

confidence: 61%

“…Genes that were differentially regulated in a statistically significant manner were classified into two groups as either up-regulated (UP) or down-regulated (DOWN) NHR-49 targets. These groups were analyzed for enrichment of gene classes based on Gene Ontology (GO) Terms using C. elegans centered publicly available online resources, Wormbase Gene Set Enrichment Analysis tool (https://wormbase.org/tools/enrichment/tea/tea.cgi) and WormCat (http://wormcat.com/) (Holdorf et al, 2020). Representation Factor was calculated at http://nemates.org/MA/progs/overlap_stats.html.…”

Section: Gene Ontology Analysesmentioning

confidence: 99%

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NHR-49 Acts in Distinct Tissues to Promote Longevity versus Innate Immunity

Naim

Amrit

Ratnappan

et al. 2020

Preprint

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Aging and immunity are inextricably linked and many genes that extend lifespan also enhance immunoresistance. However, it remains unclear if longevity-enhancing factors modulate immunity and longevity by distinct or shared mechanisms. Here, we demonstrate that the Caenorhabditis elegans pro-longevity factor, NHR-49, also promotes resistance against Pseudomonas aeruginosa, but modulates immunity and longevity by spatially and mechanistically distinct mechanisms. Fenofibrate, an agonist of NHR-49’s mammalian functional homolog, PPARα, enhanced worm immunoresistance in an NHR-49-dependent manner. NHR-49 expression is increased by germline ablation, an intervention that extends lifespan, but lowered by pathogen exposure. NHR-49 acted in multiple somatic tissues to promote longevity, whereas, it’s pro-immunity function was mediated by neuronal expression. The canonical NHR-49 target genes, acs-2 and fmo-2, were upregulated by germline loss, but infection triggered fmo-2 downregulation and acs-2 upregulation. Interestingly, neither gene conferred resistance against Gram-negative Pseudomonas, unlike their reported roles in immunity against Gram-positive pathogens. Thus, NHR-49 is differentially regulated by interventions that bring about long-term changes (lifespan extension) vs. short-term stress (pathogen exposure) and in response it orchestrates distinct outputs, including pathogen-specific transcriptional programs. Overall, our study demonstrates the independent control of immunity and longevity by a conserved regulatory protein.

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Section: Nhr-49 Widely Modulates the Expression Of Innate-immunity Genesmentioning

confidence: 61%

Section: Gene Ontology Analysesmentioning

confidence: 99%

NHR-49 Acts in Distinct Tissues to Promote Longevity versus Innate Immunity

Naim

Amrit

Ratnappan

et al. 2020

Preprint

View full text Add to dashboard Cite

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“…(G, H) gene categories enriched in CSR-1 targets (22G-RNA ≥ 150 RPM) (G) or CSR-1 interactors (H). Figures generated using WormCat (Holdorf et al, 2019) ; nascent RNAs (GRO-seq) (B); or mRNAs (RNAseq) (C); or mRNAs engaged in translation (Ribo-seq) (D), in CSR-1 KO compared to WT strain. The distribution for the CSR-1 targets with 22G-RNA in CSR-1 IP ≥ 1 RPM, ≥ 50 RPM, or ≥ 150 RPM is shown.…”

Section: (A)mentioning

confidence: 99%

Translation and codon usage regulate Argonaute slicer activity to trigger small RNA biogenesis

Singh

Cornes

et al. 2020

Preprint

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In the Caenorhabditis elegans germline, thousands of mRNAs are concomitantly expressed with antisense 22G-RNAs, which are loaded into the Argonaute CSR-1. Despite their essential functions for animal fertility and embryonic development, how CSR-1 22G-RNAs are produced remains unknown. Here, we show that CSR-1 slicer activity is primarily involved in triggering the synthesis of small RNAs on the coding sequences of germline mRNAs and post-transcriptionally regulates a fraction of targets. CSR-1-cleaved mRNAs prime the RNA-dependent RNA polymerase, EGO-1, to synthesize 22G-RNAs in phase with ribosome translation in the cytoplasm, in contrast to other 22G-RNAs mostly synthesized in germ granules. Moreover, codon optimality and efficient translation antagonize CSR-1 slicing and 22G-RNAs biogenesis. We propose that codon usage differences encoded into mRNA sequences might be a conserved strategy in eukaryotes to regulate small RNA biogenesis and Argonaute targeting.

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“…The STRING database (http://string-db.org/) is an online tool for high-throughput functional analysis of genes. In this study, the potential associations between the 12 core genes and PLK1 were assessed through the GO annotation analysis and KEGG pathway enrichment analysis [26] [27]. P-values < 0.05 were considered as statistically significance.…”

Section: Go and Kegg Analysismentioning

confidence: 99%

PLK1 Is Implicated in the Poor Prognosis of Hepatocellular Carcinoma

Xun¹,

Lu²,

Wang³

2020

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We aimed to identify if PLK1 could be used as a new diagnostic and therapeutic biomarker in hepatocellular carcinoma (HCC) patient. Expression of PLK1 in HCC was analyzed by using GEPIA (Gene Expression Profiling Interactive Analysis) and UALCAN databases. GEPIA and CBioPortal tools were applied to determine patients' survival and PLK1 mutations, respectively. PPI (Protein-Protein Interaction) networks were further built by STRING (Search Tool for the Retrieval of Interacting Genes) and Metascape Web portals. The data demonstrated that the expression of PLK1 in HCC was significantly enhanced when compared to normal liver tissues (P < 0.001). A higher PLK1 expression resulted in a remarkably shorter disease-free survival as well as overall survival. Moreover, the expression of PLK1 in HCC was related to HCC patients' grade and race, but not gender. The data also suggested that expression of PLK1 elevated gradually from stage 1 to 3 but decreased in stage 4. Three specific gene mutations K146R, S335Afs*120 and D429H of PLK1 occurred in HCC and these unique mutations were not seen in any other tumor tissues. Finally, PPI networks and GO enrichment analysis suggested that PLK1 might be associated with cell cycle and p53 signaling pathway etc. Taken together, our novel findings suggest that PLK1 is implicated in the poor prognosis of hepatocellular carcinoma.

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WormCat: an online tool for annotation and visualization of Caenorhabditis elegans genome-scale data

Abstract: 1

Cited by 38 publications

References 18 publications

NHR-49 Acts in Distinct Tissues to Promote Longevity versus Innate Immunity

NHR-49 Acts in Distinct Tissues to Promote Longevity versus Innate Immunity

Translation and codon usage regulate Argonaute slicer activity to trigger small RNA biogenesis

PLK1 Is Implicated in the Poor Prognosis of Hepatocellular Carcinoma

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