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The molecular effects of cordycepin on RNA synthesis in Saccharomyces cerevisiae

ABSTRACT: Cordycepin (3’ deoxyadenosine) is a biologically active compound that, when incorporated during RNA synthesis in vitro, provokes chain termination due to the absence of a 3’ hydroxyl moiety. We were interested in the effects mediated by this drug in vivo and analysed its impact on RNA metabolism of yeast. Our results support the view that cordycepin-triphosphate (CoTP) is the toxic component that is limiting cell growth through inhibition of RNA synthesis. Unexpectedly, cordycepin treatment modulated 3’ end heterogeneity of ACT1 and ASC1 mRNAs and rapidly induced extended transcripts derived from CYH2 and NEL025c loci. Moreover, cordycepin ameliorated the growth defects of poly(A) polymerase mutants and the pap1-1 mutation neutralized the effects of the drug on gene expression. Our observations are consistent with an epistatic relationship between poly(A) polymerase function and cordycepin action and suggest that a major mode of cordycepin activity reduces 3’ end formation efficiency independently of its potential to terminate RNA chain elongation. Finally, chemical-genetic profiling revealed genome-wide pathways linked to cordycepin activity and identified novel genes involved in poly(A) homeostasis. Keywords: response to drug treatment

ORGANISM(S): Saccharomyces cerevisiae

PROVIDER: GSE14619 | GEO | 2009/01/30

SECONDARY ACCESSION(S): PRJNA112319

REPOSITORIES: GEO

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The molecular effects of cordycepin on RNA synthesis in Saccharomyces cerevisiae

Project description:Cordycepin (3â deoxyadenosine) is a biologically active compound that, when incorporated during RNA synthesis in vitro, provokes chain termination due to the absence of a 3â hydroxyl moiety. We were interested in the effects mediated by this drug in vivo and analysed its impact on RNA metabolism of yeast. Our results support the view that cordycepin-triphosphate (CoTP) is the toxic component that is limiting cell growth through inhibition of RNA synthesis. Unexpectedly, cordycepin treatment modulated 3â end heterogeneity of ACT1 and ASC1 mRNAs and rapidly induced extended transcripts derived from CYH2 and NEL025c loci. Moreover, cordycepin ameliorated the growth defects of poly(A) polymerase mutants and the pap1-1 mutation neutralized the effects of the drug on gene expression. Our observations are consistent with an epistatic relationship between poly(A) polymerase function and cordycepin action and suggest that a major mode of cordycepin activity reduces 3â end formation efficiency independently of its potential to terminate RNA chain elongation. Finally, chemical-genetic profiling revealed genome-wide pathways linked to cordycepin activity and identified novel genes involved in poly(A) homeostasis. Keywords: response to drug treatment Each experiment was performed as triplicate. We analyzed RNA obtained from wild-type cells, from wild-type cells treated with 40 microgram/ml cordycepin for 1 hour, from pap1-1 mutant cells grown at permissive temperature (25Â°C) and from pap1-1 mutant cells grown at permissive temperature (25Â°C) treated with 40 microgram/ml cordycepin for 1 hour.

2010-05-06 | E-GEOD-14619 | biostudies-arrayexpress

The anti-cancer effects of cordycepin in MA-10 mouse laydig tumor cells

Project description:Cordycepin, a 3-deoxyadenosine, a traditional Chinese medicine. Studies have demonstrated that cordycepin could modulate multiple signaling pathways to induce cancer cell death. This study aims to determine the genes regulated by Cordycepin and clarify the possible molecular mechanism underlying their action.

2019-05-24 | GSE112513 | GEO

Genetic and pharmacological evidence for kinetic competition between alternative poly(A) sites in yeast - cordycepin treatment

Project description:PAT-seq approach was used to determine changes to 3'UTR length in yeast upon addition of 20µg/ml cordycepin (3'deoxyadenosine) for 0, 5, 10, 20 or 40 minutes

2021-06-25 | GSE160537 | GEO

Synergistic effect of CD47 blockade in combination with cordycepin treatment against cancer

Project description:Cordycepin was widely considered as a direct tumor-suppressive drug, however, and as of now few studies have been presented to investigate the effect of cordycepin therapy to the tumor microenvironment (TME). In our study, we demonstrated that cordycepin would decrease the function of M1-like macrophage in TME, and also contribute to macrophage polarization (M2-macrophage). Herein, we tried to establish a combined therapeutic strategy of cordycepin and anti-CD47 antibody. Using single cell RNA sequencing, we improved that the combined treatment would significantly increase the effect of cordycepin, which would reactivate macrophages and reverse macrophage polarization. And then, the combined treatment would regulate the proportion of CD8+T cells to increase the PFS for digestive tract malignancy patients. Finally, Flow cytometry was used to validate the change of percentage for TAM and TIL. Our finding suggests the combined treatment of cordycepin and anti-CD47 mAb could significantly increase tumor suppression, which could increase M1-macrophage and decrease M2-macrophage. The PFS for digestive tract malignancy patients would be increased though regulation of CD8+T cells.

2023-03-30 | GSE224945 | GEO

ChIP-seq from Human U2OS Cell for CRY2 and RUVBL2 with DMSO or Cordycepin Treatment

Project description:To evaluate the effects of cordycepin on CRY2 and RUVBL2 binding on the chromatin sites, non-synchronized U2OS cells were treated with cordycepin (100 uM) for 1 h, then performed ChIP-seq. We found that cordycepin relieves CRY2 and RUVBL2 proteins from the chromatin for more than 60-70%.

2020-05-07 | GSE130507 | GEO

ChIP-seq from Human U2OS Cell for BMAL1 and CRY1 with DMSO or Cordycepin Treatment

Project description:To evaluate the effects of cordycepin on CRY1 and BMAL1 binding on the chromatin sites, non-synchronized U2OS cells were treated with cordycepin (100 uM) for 1 h, then performed ChIP-seq. We found cordycepin relieves CRY1 proteins from the chromatin for more than 60-70%, while unaffects BMAL1 from the chromatin.

2020-05-07 | GSE130506 | GEO

Cordycepin Delays Postovulatory Aging of Mammalian Oocytes through Inhibition of Maternal mRNAs Degradation via DCP1A Polyadenylation Suppression

Project description:Postovulatory aging leads to the decline in oocyte quality and subsequent impairment of embryonic development, thereby reducing the success rates of assisted reproductive technology (ART). Nevertheless, potential preventative strategies to improve aging oocytes quality and the associated underlying mechanisms warrant further investigation. In this study, we identify cordycepin, an natural nucleoside analogue, as having the potential to restore the postovulatory aging-induced decline in oocyte quality, including aspects such as oocyte fragmentation, embryonic developmental competence, spindle/chromosomes morphology and mitochondrial function. Proteomic and RNA sequencing analyses revealed that cordycepin inhibited the degradation of several crucial maternal proteins and mRNAs caused by aging. Mechanistically, cordycepin was found to suppress the elevation of DCP1A protein levels by inhibiting polyadenylation during postovulatory aging, consequently impeding the decapping of maternal mRNAs. In humans, the increased degradation of DCP1A and total mRNA during aging was also inhibited by cordycepin. Collectively, our findings demonstrate that cordycepin may prevent postovulatory aging of mammalian oocytes by inhibition of maternal mRNAs degradation via DCP1A polyadenylation suppression, thereby promoting the successful rates of ART procedure.

2024-01-26 | PXD042600 | Pride

Effects of cordycepin on murine macrophage-like cells in the presence and absence of an inflammatory stimulus

Project description:To perform high-throughput, transcriptome-wide analysis on RAW 264.7 cells treated with cordycepin with and without bacterial lipopolysaccharide (LPS) to investigate cordycepin's anti-inflammatory properties and determine whether particular classes of RNAs were sensitive to cordycepin.

2019-02-07 | GSE126157 | GEO

Genetic and pharmacological evidence for kinetic competition between alternative poly(A) sites in yeast - 4tU cordycepin treatment with rpb1 slow mutant

Project description:mPAT approach using an anchored oligo-dT (TV12VN) primer to determine changes to 3'UTR length in yeast with a slow RNA polymerase II mutant rpb1-1, complemented with wild-type RPB1 or a slow rpb1 mutant plasmid, upon cordycepin treatment and new transcription using 4-thiouracil (4tU) labelling of RNA. This appears as a T to C conversion in sequencing reads.

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Project description:bra-inra09-01_bioen - cordycepin - Diversification of the Molecular Mechanisms Involved in the Control of the Energetic Balance in Angiosperms - To evaluate the importance of mRNA stability control in glucose signaling, genome wide RNA transcript levels changes will be evaluated in response to short term treatments with glucose or glucose plus abscisic acid (ABA) under conditions of transcriptional inhibition in Arabidopsis. The underlying mechanisms will be investigated for a selected number of co-regulated genes (transcription factors, kinases). 12 dye-swap - treatment variations

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