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Transcriptome analysis of toosendanin (TSN)-treated DLBCL cells

ABSTRACT: The effects of TSN on total RNA expression were tested in DOHH2 cells using RNA-seq

ORGANISM(S): Homo sapiens

PROVIDER: GSE271299 | GEO | 2024/07/07

REPOSITORIES: GEO

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Transcriptome analysis of toosendanin (TSN)-treated macrophages

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Project description:Tudor staphylococcal nuclease (TSN or Tudor-SN; also known as SND1) is an evolutionarily conserved protein involved in transcriptional and post-transcriptional regulation of gene expression in animals. Although TSN was found to be indispensable for normal plant development and stress tolerance, the molecular mechanisms underlying these functions remain elusive. Here we show that Arabidopsis thaliana TSN is essential for integrity and function of cytoplasmic messenger ribonucleoprotein (mRNP) complexes called stress granules (SG) and processing bodies (PB), sites of post-transcriptional gene regulation during stress. TSN associates with SG following their microtubule-dependent assembly and plays a scaffolding role in both SG and PB. The enzymatically active tandem repeat of four SN domains is crucial for targeting TSN to the cytoplasmic mRNA complexes, and is sufficient for the cytoprotective function of TSN during stress. Furthermore, our work connects the cytoprotective function of TSN with its positive role in stress-induced mRNA decapping. While stress led to a pronounced increase in the accumulation of uncapped mRNAs in wild type plants, this increase was abrogated in TSN knockout plants. Taken together, our results establish TSN as a key enzymatic component of catabolic machinery responsible for the processing of mRNAs in the cytoplasmic mRNP complexes during stress.

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Project description:Residue-specific arginine methylation (meR) on the E2F1 subunit plays an essential role in determining whether cell cycle progression or apoptosis ensues, although the molecular pathways underpinning the effects of methylation remain obscure. We report here that the methylation events on E2F1 have a direct impact on the mechanisms which underpin gene expression control. Specifically, the PRMT5-mediated symR mark not only influences the transcription repertoire of genes targeted by E2F1, but also endows E2F1 with the ability to regulate RNA splicing. This occurs through tudor domain protein p100/TSN which reads the symR mark on E2F1, and thereby enables a distinct set of RNA to be alternatively spliced. The p100/TSN-E2F1 complex binds alternatively spliced RNAs, with many RNAs derived from E2F target genes connected with proliferation and cancer.

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