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Identification of pararosaniline as a modifier of RNA splicing in Caenorhabditis elegans.

Dylan Huynh | Cheng-Wei Wu
G3 (Bethesda, Md.) | 2023

Posttranscriptional splicing of premessenger RNA (mRNA) is an evolutionarily conserved eukaryotic process for producing mature mRNA that is translated into proteins. Accurate splicing is necessary for normal growth and development, and aberrant splicing is increasingly evident in various human pathologies. To study environmental factors that influence RNA splicing, we employed a fluorescent Caenorhabditis elegans in vivo splicing reporter as a biomarker for splicing fidelity to screen against the US EPA ToxCast chemical library. We identified pararosaniline hydrochloride as a strong modifier of RNA splicing. Through gene expression analysis, we found that pararosaniline activates the oxidative stress response and alters the expression of key RNA splicing regulator genes. Physiological assays show that pararosaniline is deleterious to C. elegans development, reproduction, and aging. Through a targeted RNAi screen, we found that inhibiting protein translation can reverse pararosaniline's effect on the splicing reporter and provide significant protection against long-term pararosaniline toxicity. Together, this study reveals a new chemical modifier of RNA splicing and describes translation inhibition as a genetic mechanism to provide resistance.

Pubmed ID: 37852248

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This is a list of tools and resources that we have found mentioned in this publication.


Caenorhabditis Genetics Center (tool)

RRID:SCR_007341

Center that acquires, maintains, and distributes genetic stocks and information about stocks of the small free-living nematode Caenorhabditis elegans for use by investigators initiating or continuing research on this genetic model organism. A searchable strain database, general information about C. elegans, and links to key Web sites of use to scientists, including WormBase, WormAtlas, and WormBook are available.

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Caenorhabditis elegans with no genotype reported (organism)

RRID:WB-STRAIN:WBStrain00054619

Caenorhabditis elegans with name EMPTY from WB.

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(raga-1(ok386) II; lin-15(n765)ybIs2167[eft-3p::ret-1E4E5(+1) E6-GGS6-mCherry+eft-3p::ret-1E4E5(+1) E6(+2)GGS6-GFP+ lin-15(+)+pRG5271Neo] X) (organism)

RRID:WB-STRAIN:WBStrain00062120

Caenorhabditis elegans with name (raga-1(ok386) II; lin-15(n765)ybIs2167[eft-3p::ret-1E4E5(+1) E6-GGS6-mCherry+eft-3p::ret-1E4E5(+1) E6(+2)GGS6-GFP+ lin-15(+)+pRG5271Neo] X) from WB.

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N2 (organism)

RRID:WB-STRAIN:WBStrain00000001

Caenorhabditis elegans with name Caenorhabditis elegans wild isolate. from WB.

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Caenorhabditis elegans with no genotype reported (organism)

RRID:WB-STRAIN:WBStrain00054618

Caenorhabditis elegans with name EMPTY from WB.

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Caenorhabditis elegans with no genotype reported (organism)

RRID:WB-STRAIN:WBStrain00054618

Caenorhabditis elegans with name EMPTY from WB.

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(raga-1(ok386) II; lin-15(n765)ybIs2167[eft-3p::ret-1E4E5(+1) E6-GGS6-mCherry+eft-3p::ret-1E4E5(+1) E6(+2)GGS6-GFP+ lin-15(+)+pRG5271Neo] X) (organism)

RRID:WB-STRAIN:WBStrain00062120

Caenorhabditis elegans with name (raga-1(ok386) II; lin-15(n765)ybIs2167[eft-3p::ret-1E4E5(+1) E6-GGS6-mCherry+eft-3p::ret-1E4E5(+1) E6(+2)GGS6-GFP+ lin-15(+)+pRG5271Neo] X) from WB.

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Caenorhabditis elegans with no genotype reported (organism)

RRID:WB-STRAIN:WBStrain00054620

Caenorhabditis elegans with name EMPTY from WB.

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