Ssu72 phosphatase is essential for thermogenic adaptation by regulating cytosolic translation
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ABSTRACT:
PROVIDER: PRJNA930671 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Brown adipose tissue (BAT) plays a pivotal role in maintaining body temperature and energy homeostasis. To identify the fuction of Ssu72 phosphatase in BAT thermogenesis, we analyzed gene expression of BAT from SSU72 WT and SSU72aKO.
2023-02-27 | GSE224337 | GEO
Project description:Brown adipose tissue (BAT) plays a pivotal role in maintaining body temperature and energy homeostasis. BAT dysfunction is associated with impaired metabolic health. Here, we show that Ssu72 phosphatase is essential for mRNA translation of genes required for thermogenesis in BAT. Ssu72 is found to be highly expressed in BAT among adipose tissue depots, and the expression level of Ssu72 is increased upon acute cold exposure. Mice lacking adipocyte Ssu72 exhibit cold intolerance during acute cold exposure. Mechanistically, Ssu72 deficiency alters cytosolic mRNA translation program through hyperphosphorylation of eIF2α and reduces translation of mitochondrial oxidative phosphorylation (OXPHOS) subunits, resulting in mitochondrial dysfunction and defective thermogenesis in BAT. In addition, metabolic dysfunction in Ssu72-deficient BAT returns to almost normal after restoring Ssu72 expression. In summary, our findings demonstrate that cold-responsive Ssu72 phosphatase is involved in cytosolic translation of key thermogenic effectors via dephosphorylation of eIF2α in brown adipocytes, providing insights into metabolic benefits of Ssu72.
| S-EPMC9968297 | biostudies-literature
Project description:Ssu72 is a Ser5P-RNAPII phosphatase, nevertheless few targets have been characterized and its role in mammal cells remains elusive. Using ChIPseq and GROseq technologies we aimed to identify Ssu72 targets in human embryonic stem cells.
2014-11-01 | GSE61393 | GEO
Project description:We report accumulation of cryptic antisense transcripts in ssu72 mutant cells. A histone deacetylase (Hos2) is not required to repress the cryptic transcription in SSU72+ strain however in ssu72 mutant cells, Hos2 has an important role in suppression of the cryptic transcription Phosphorylation of the RNA polymerase II C-terminal domain on heptad Y1S2P3T4S5P6S7 coordinates key events during transcription and when its deregulation leads to defects in transcription and RNA processing. Here we report that histone deacetylase complex activity of the fission yeast Hos2/Set3 complex plays an important role in suppressing cryptic initiation of the antisense transcription when the C-terminal domain phosphorylation is dysregulated due to the loss of Ssu72 phosphatase. Interestingly, while single hos2/set3 mutants have little effect, loss of hos2 or set3 in addition to ssu72? leads to synergistic increase in antisense transcription globally and correlates with increases genomic instability and formation of deleterious R-loop structures across these regions. We propose that Ssu72 is essential to suppress initiation of cryptic transcription in the 3?end of the RNA polymerase II transcribed regions. In the absence of Ssu72, antisense transcription is supressed by the Hos2/Set3 dependent surveillance mechanism to maintain genome stability.
2020-06-30 | GSE144591 | GEO
Project description:We report accumulation of cryptic antisense transcripts in ssu72 mutant cells. A histone deacetylase (Hos2) is not required to repress the cryptic transcription in SSU72+ strain however in ssu72 mutant cells, Hos2 has an important role in suppression of the cryptic transcription Phosphorylation of the RNA polymerase II C-terminal domain on heptad Y1S2P3T4S5P6S7 coordinates key events during transcription and when its deregulation leads to defects in transcription and RNA processing. Here we report that histone deacetylase complex activity of the fission yeast Hos2/Set3 complex plays an important role in suppressing cryptic initiation of the antisense transcription when the C-terminal domain phosphorylation is dysregulated due to the loss of Ssu72 phosphatase. Interestingly, while single hos2/set3 mutants have little effect, loss of hos2 or set3 in addition to ssu72? leads to synergistic increase in antisense transcription globally and correlates with increases genomic instability and formation of deleterious R-loop structures across these regions. We propose that Ssu72 is essential to suppress initiation of cryptic transcription in the 3?end of the RNA polymerase II transcribed regions. In the absence of Ssu72, antisense transcription is supressed by the Hos2/Set3 dependent surveillance mechanism to maintain genome stability.
2020-06-30 | GSE144592 | GEO
Project description:Adaptive thermogenesis has attracted much attention because of its ability to raise systemic energy expenditure and counter obesity and diabetes. Recent data have indicated that thermogenic fat cells utilize creatine to stimulate futile substrate cycling, dissipating chemical energy as heat. This model was based on the super-stoichiometric relationship between creatine added to mitochondria and O2 consumed, and this project aims at providing direct evidence for the molecular basis of this futile creatine cycling activity. In this project, we found that thermogenic fat cells contain robust phosphocreatine hydrolase (PCr’ase) activity, attributable to tissue-nonspecific alkaline phosphatase (TNAP), which was identified by the quantitative mass spectrometric analysis of a purified mitochondrial protein fraction containing the PCr’ase activity. TNAP hydrolyzes phosphocreatine to initiate a futile cycle of creatine dephosphorylation and phosphorylation; it is localized to mitochondria of thermogenic fat cells, where the futile creatine cycling occurs. Furthermore, we demonstrated in this project the essential role of TNAP in activating the futile creatine cycling and increasing whole body energy expenditure using genetic and pharmacological approaches. We also found that the genetic depletion of TNAP in murine adipose tissue causes rapid-onset obesity, with no change in movement or feeding behavior of the animals. Using quantitative mass spectrometry, we showed that genetic depletion of TNAP causes an upregulation of UCP1, as well as other proteins involved in oxidative metabolism, to compensate for a dampened thermogenesis. In summary, the data we acquired in this project illustrate the critical role of TNAP as a phosphocreatine phosphatase in the futile creatine cycling and adipose thermogenesis.
2022-02-17 | PXD025032 | Pride
Project description:Ssu72 is a Ser5P-RNAPII phosphatase, nevertheless few targets have been characterized and its role in mammal cells remains elusive. Using ChIPseq and GROseq technologies we aimed to identify Ssu72 targets in human embryonic stem cells. For the ChIPseq experiments, H1 hESCs growing in mTeSR media were doubled fixed with DSG 2mM (45min) and FA 1% (20min) and processed to chromatin immunoprecipitation. For GROseq experiments, H1 hESCs were transfected with siCtrl or siSsu72 siRNAs using RNAimax (Invitrogene) for 48h. Then, run-on experiment was done with isolated nuclei. Nascent RNA purification and subsequent steps needed before sequencing were carried out essentially as described in Core et al, 2008, Science 319(5871): 1791-1792.
2014-11-01 | E-GEOD-61393 | biostudies-arrayexpress
Project description:Deletion of ssu72 gene leads to a transcription elongation defect and the increase in the level of Ser5 and Ser7 phosphorylation in CTD of Rpb1 Phosphorylation of the RNA polymerase II C-terminal domain on heptad Y1S2P3T4S5P6S7 coordinates key events during transcription and when its deregulation leads to defects in transcription and RNA processing. Here we report that histone deacetylase complex activity of the fission yeast Hos2/Set3 complex plays an important role in suppressing cryptic initiation of the antisense transcription when the C-terminal domain phosphorylation is dysregulated due to the loss of Ssu72 phosphatase. Interestingly, while single hos2/set3 mutants have little effect, loss of hos2 or set3 in addition to ssu72? leads to synergistic increase in antisense transcription globally and correlates with increases genomic instability and formation of deleterious R-loop structures across these regions. We propose that Ssu72 is essential to suppress initiation of cryptic transcription in the 3?end of the RNA polymerase II transcribed regions. In the absence of Ssu72, antisense transcription is supressed by the Hos2/Set3 dependent surveillance mechanism to maintain genome stability.
2020-06-30 | GSE144594 | GEO
Project description:Deletion of ssu72 gene leads to a transcription elongation defect and the increase in the level of Ser5 and Ser7 phosphorylation in carboxy-terminal domain (CTD) of Rpb1 Phosphorylation of the RNA polymerase II C-terminal domain on heptad Y1S2P3T4S5P6S7 coordinates key events during transcription and when its deregulation leads to defects in transcription and RNA processing. Here we report that histone deacetylase complex activity of the fission yeast Hos2/Set3 complex plays an important role in suppressing cryptic initiation of the antisense transcription when the C-terminal domain phosphorylation is dysregulated due to the loss of Ssu72 phosphatase. Interestingly, while single hos2/set3 mutants have little effect, loss of hos2 or set3 in addition to ssu72? leads to synergistic increase in antisense transcription globally and correlates with increases genomic instability and formation of deleterious R-loop structures across these regions. We propose that Ssu72 is essential to suppress initiation of cryptic transcription in the 3?end of the RNA polymerase II transcribed regions. In the absence of Ssu72, antisense transcription is supressed by the Hos2/Set3 dependent surveillance mechanism to maintain genome stability.
2020-06-30 | GSE144593 | GEO
Project description:To investigate how mammalian Ssu72 regulated gene expression, we performed RNA-Seq analyses of Ssu72 in three different cell types depending on their proliferation capabilities: embryonic stem (ES) cells (highly proliferating), primary murine embryonic fibroblasts (MEFs) (moderate proliferating), and hepatocytes (almost quiescent). Ssu72 deletion was induced by infection with Cre recombinase adenovius (Ad-Cre). Infection of ESf/f, MEFf/f, and hepatocytef/f with Ad-Cre resulted in efficient reduction of Ssu72 levels. Depletion of Ssu72 resulted in downregulation or upregulation of large subsets of genes in three different cell types.
2020-12-28 | GSE122101 | GEO