Tho2-mediated escort of Nrd1 regulates gene expression for lifespan maintenance
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1085260 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR28258340_1.fastq.gz | Fastqsanger.gz | |||
| SRR28258340_2.fastq.gz | Fastqsanger.gz | |||
| SRR28258341_1.fastq.gz | Fastqsanger.gz | |||
| SRR28258341_2.fastq.gz | Fastqsanger.gz | |||
| SRR28258342_1.fastq.gz | Fastqsanger.gz |
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Project description:The relationship between aging and RNA biogenesis and trafficking is attracting growing interest, yet the precise mechanisms are unknown. The THO complex is crucial for mRNA cotranscriptional maturation and export. Herein, we report that the THO complex is closely linked to maintaining a normal lifespan. Deficiencies in Hpr1 and Tho2, components of the THO complex, reduced replicative lifespan (RLS) and are linked to a novel Sir2-independent RLS control pathway. Although transcript sequestration in hpr1Δ or tho2Δ mutants was countered by exosome component Rrp6, loss of this failed to mitigate RLS defects in hpr1Δ. However, RLS impairment in tho2Δ was counteracted by Nrd1-specific mutants that interacted with Rrp6. This effect relied on the interaction of Nrd1, a transcriptional regulator of aging-related genes, including ribosome biogenesis or RNA metabolism genes, with RNA polymerase II. Nrd1 overexpression reduced RLS in a Tho2-dependent pathway. Intriguingly, THO2 deletion mirrored Nrd1 overexpression effects by inducing arbitrary Nrd1 chromatin binding. Taken together, these findings underscore the importance of Tho2-mediated Nrd1 escorting in maintaining a normal lifespan by transcriptional regulation of aging-related genes.
2024-08-21 | GSE262156 | GEO
Project description:The relationship between aging and RNA biogenesis and trafficking is attracting growing interest, yet the precise mechanisms are unknown. The THO complex is crucial for mRNA cotranscriptional maturation and export. Herein, we report that the THO complex is closely linked to maintaining a normal lifespan. Deficiencies in Hpr1 and Tho2, components of the THO complex, reduced replicative lifespan (RLS) and are linked to a novel Sir2-independent RLS control pathway. Although transcript sequestration in hpr1Δ or tho2Δ mutants was countered by exosome component Rrp6, loss of this failed to mitigate RLS defects in hpr1Δ. However, RLS impairment in tho2Δ was counteracted by Nrd1-specific mutants that interacted with Rrp6. This effect relied on the interaction of Nrd1, a transcriptional regulator of aging-related genes, including ribosome biogenesis or RNA metabolism genes, with RNA polymerase II. Nrd1 overexpression reduced RLS in a Tho2-dependent pathway. Intriguingly, THO2 deletion mirrored Nrd1 overexpression effects by inducing arbitrary Nrd1 chromatin binding. Taken together, these findings underscore the importance of Tho2-mediated Nrd1 escorting in maintaining a normal lifespan by transcriptional regulation of aging-related genes.
2024-08-21 | GSE261087 | GEO
Project description:Tho2-mediated escort of Nrd1 regulates gene expression for lifespan maintenance
| PRJNA1090488 | ENA
Project description:The relationship between aging and RNA biogenesis and trafficking is attracting growing interest, yet the precise mechanisms are unknown. The THO complex is crucial for mRNA cotranscriptional maturation and export. Herein, we report that the THO complex is closely linked to the regulation of lifespan. Deficiencies in Hpr1 and Tho2, components of the THO complex, reduced replicative lifespan (RLS) and are linked to a novel Sir2-independent RLS control pathway. Although transcript sequestration in hpr1Δ or tho2Δ mutants was countered by exosome component Rrp6, loss of this failed to mitigate RLS defects in hpr1Δ. However, RLS impairment in hpr1Δ or tho2Δ was counteracted by the additional expression of Nrd1-specific mutants that interacted with Rrp6. This effect relied on the interaction of Nrd1, a transcriptional regulator of aging-related genes, including ribosome biogenesis or RNA metabolism genes, with RNA polymerase II. Nrd1 overexpression reduced RLS in a Tho2-dependent pathway. Intriguingly, Tho2 deletion mirrored Nrd1 overexpression effects by inducing arbitrary Nrd1 chromatin binding. Furthermore, our genome-wide ChIP-seq analysis revealed an increase in the recruitment of Nrd1 to translation-associated genes, known to be related to aging, upon Tho2 loss. Taken together, these findings underscore the importance of Tho2-mediated Nrd1 escorting in the regulation of lifespan pathway through transcriptional regulation of aging-related genes.
| S-EPMC11320360 | biostudies-literature
Project description:The mechanistic connection between the THO/TREX complex and RdDM remains poorly understood. To address this, we performed EMS mutagenesis in a transgenic Col-0 background harboring pro2×35S::LUC and pro2×35S::NPTII reporters and homozygous for rdr6, and identified a low-fluorescence mutant, tho2-8. Unlike null alleles, tho2-8 is a viable homozygous allele, offering a unique opportunity to explore THO2 function in DNA methylation. Here, we report that THO2 is required for proper siRNA accumulation and RdDM activity, revealing a previously uncharacterized role for the THO/TREX complex in epigenetic gene silencing. This study expands our understanding of the molecular coordination between RNA metabolism and epigenetic regulation in plants.
2025-09-07 | GSE304222 | GEO
Project description:The mechanistic connection between the THO/TREX complex and RdDM remains poorly understood. To address this, we performed EMS mutagenesis in a transgenic Col-0 background harboring pro2×35S::LUC and pro2×35S::NPTII reporters and homozygous for rdr6, and identified a low-fluorescence mutant, tho2-8. Unlike null alleles, tho2-8 is a viable homozygous allele, offering a unique opportunity to explore THO2 function in DNA methylation. Here, we report that THO2 is required for proper siRNA accumulation and RdDM activity, revealing a previously uncharacterized role for the THO/TREX complex in epigenetic gene silencing. This study expands our understanding of the molecular coordination between RNA metabolism and epigenetic regulation in plants.
2025-09-07 | GSE304227 | GEO
Project description:The mechanistic connection between the THO/TREX complex and RdDM remains poorly understood. To address this, we performed EMS mutagenesis in a transgenic Col-0 background harboring pro2×35S::LUC and pro2×35S::NPTII reporters and homozygous for rdr6, and identified a low-fluorescence mutant, tho2-8. Unlike null alleles, tho2-8 is a viable homozygous allele, offering a unique opportunity to explore THO2 function in DNA methylation. Here, we report that THO2 is required for proper siRNA accumulation and RdDM activity, revealing a previously uncharacterized role for the THO/TREX complex in epigenetic gene silencing. This study expands our understanding of the molecular coordination between RNA metabolism and epigenetic regulation in plants.
2025-09-07 | GSE304225 | GEO
Project description:In order to dissect the nuclear RNA quality control (QC) mechanisms, we used a powerful assay based on global perturbation of mRNP biogenesis in yeast Saccharomyces cerevisiae by the bacterial Rho helicase. We have monitored the recruitment of THO complex subunit upon Rho activation, which revealed that Tho2 was over-recruited in opposition to its counterparts. We then tracked the recruitment of Rrp6 upon Rho induction in WT strain and in strains lacking either Mft1 or Tho2, showing the implication of Tho2 in Rrp6 recruitment over Rho induction. Finally, we measured the recruitment of Rrp6 upon partial deletion of Tho2 C-terminal domain responsible for its RNA interaction ability, proving that Tho2 presence on the chromatin is required for the Rho-induced Rrp6 recruitment..
2023-04-30 | E-MTAB-12378 | biostudies-arrayexpress
Project description:Tho2 protein was tagged with a TAP tag and the gene expression profile was compared to an untagged wildtype strain of the same background using DNA microarrays
2013-09-24 | E-MTAB-1892 | biostudies-arrayexpress