Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA138985 | ENA |
REPOSITORIES: ENA
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Project description:Protein translation factors play crucial roles in a variety of stress responses. Here, we show that the eukaryotic elongation factor 1Bdelta (eEF1Bdelta) changes its structure and function from a translation factor into a heat shock response transcription factor by alternative splicing. While eEF1Bdelta is specifically localized in the cytoplasm, the long isoform of eEF1Bdelta (eEF1BdeltaL) is localized in the nucleus and induces heat shock element (HSE)-containing genes in cooperation with heat-shock transcription factor 1 (HSF1). Moreover, the N-terminal domain of eEF1BdeltaL binds with NF-E2-related factor 2 (Nrf2) and induces stress response heme oxygenase 1 (HO-1). Specific inhibition of eEF1BdeltaL with siRNA completely inhibits Nrf2-dependent HO-1 induction. In addition, eEF1BdeltaL directly binds to HSE oligo DNA in vitro and associates with HSE containing the HO-1-enhancer region in vivo. Thus, the transcriptional role of eEF1BdeltaL could provide new insights into the molecular mechanism of stress responses. We performed microarray analysis to compare the gene expression induced by eEF1Bdelta1 or eEF1BdeltaL overexpression. HEK293 cells transfected with expression plasmids encoding flag-tagged-eEF1Bdelta1 or eEF1BdeltaL protein
2011-04-12 | E-GEOD-28506 | biostudies-arrayexpress
Project description:Protein translation factors play crucial roles in a variety of stress responses. Here, we show that the eukaryotic elongation factor 1Bdelta (eEF1Bdelta) changes its structure and function from a translation factor into a heat shock response transcription factor by alternative splicing. While eEF1Bdelta is specifically localized in the cytoplasm, the long isoform of eEF1Bdelta (eEF1BdeltaL) is localized in the nucleus and induces heat shock element (HSE)-containing genes in cooperation with heat-shock transcription factor 1 (HSF1). Moreover, the N-terminal domain of eEF1BdeltaL binds with NF-E2-related factor 2 (Nrf2) and induces stress response heme oxygenase 1 (HO-1). Specific inhibition of eEF1BdeltaL with siRNA completely inhibits Nrf2-dependent HO-1 induction. In addition, eEF1BdeltaL directly binds to HSE oligo DNA in vitro and associates with HSE containing the HO-1-enhancer region in vivo. Thus, the transcriptional role of eEF1BdeltaL could provide new insights into the molecular mechanism of stress responses. We performed microarray analysis to compare the gene expression induced by eEF1Bdelta1 or eEF1BdeltaL overexpression.
2011-04-12 | GSE28506 | GEO
Project description:RNA polymerase II (Pol II) is generally paused at promoter-proximal regions in most metazoans, and based on in vitro studies, this function has been attributed to the negative elongation factor (NELF). Here, we show that upon rapid depletion of NELF, Pol II fails to be released into gene bodies, stopping instead around the +1 nucleosomal dyad-associated region. The transition to the 2nd pause region is independent of positive transcription elongation factor P-TEFb. During the heat shock response, Pol II is rapidly released from pausing at heat shock induced genes, while most genes are paused and transcriptionally downregulated during the heat shock response. We find that both aspects of the heat shock response remain intact upon NELF loss. We find that NELF depletion results in global loss of cap-binding complex from chromatin without global reduction of nascent transcript 5’ cap stability. Thus, our studies implicate NELF functioning in early elongation complexes distinct from Pol II pause-release.
2020-03-09 | GSE144786 | GEO
Project description:ZmDREB2A is a DREB2-type transcription factor cloned from maize, whose transcript was upregulated by drought, high salt, low temperature and heat stresses. The ZmDREB2A gene possesses two kinds of transcription forms by alternative splicing. Only the functional form was studied to be highly induced by stresses. Transgenic plants overexpressing ZmDREB2A (35S:ZmDREB2A) showed dwarfism and enhanced drought stress tolerance. Microarray analysis of two independent transgenic plants revealed that in addition to genes encoding LEA proteins, some genes related to heat shock and detoxification were also upregulated. Experiments on termotolerance tests of these transgenic plants showed overexpressing ZmDREB2A gene also improved plant tolerance to heat stress.
2007-04-11 | E-MEXP-819 | biostudies-arrayexpress
Project description:Human Negative Elongation Factor Activates Transcription and Regulates Alternative Transcription Initiation
| PRJNA122633 | ENA
Project description:Complex functional coupling exists between transcriptional elongation and pre-mRNA alternative splicing. Pausing sites and changes in the rate of transcription by RNAPII may therefore have a fundamental impact in the regulation of alternative splicing. Here, we show that the elongation and splicing-related factor TCERG1 regulates alternative splicing of the apoptosis gene Bcl-x in a promoter-dependent manner. TCERG1 promotes the splicing of the short isoform of Bcl-x (Bcl-xs) through the SB1 regulatory element located in the first half of exon 2. Consistent with these results, we show evidence for in vitro and in vivo interaction of TCERG1 with the Bcl-x pre-mRNA. Transcription profile analysis reveals that the RNA sequences required for the effect of TCERG1 on Bcl-x alternative splicing coincide with a putative polymerase pause site. Furthermore, TCERG1 modifies the impact of a slow polymerase on Bcl-x alternative splicing. In support of a role for an elongation mechanism in the transcriptional control of Bcl-x alternative splicing, we found that TCERG1 modifies the amount of pre-mRNAs generated at distal regions of the endogenous Bcl-x. Most importantly, TCERG1 affects the rate of RNAPII transcription of endogenous human Bcl-x. We propose that TCERG1 modulates the elongation rate of RNAPII to relieve pausing, thereby activating the pro-apoptotic Bcl-xS 5’ splice site. ChIP-Seq
2012-01-12 | E-GEOD-33716 | biostudies-arrayexpress
Project description:Proteotoxic stress such as heat shock causes heat-shock factor (HSF)-dependent transcriptional upregulation of chaperones. Heat shock also leads to a rapid and reversible downregulation of many genes, a process we term stress-induced transcriptional attenuation (SITA). The mechanism underlying this conserved phenomenon is unknown. Here we report that enhanced recruitment of negative transcription elongation factors to gene promoters in human cell lines induces SITA. A chemical inhibitor screen showed that active translation and protein ubiquitination are required for the response. We further find that proteins translated during heat shock are subjected to ubiquitination and that p38 kinase signaling connects cytosolic translation with gene downregulation. Notably, brain samples of subjects with Huntington's disease also show transcriptional attenuation, which is recapitulated in cellular models of protein aggregation similar to heat shock. Thus our work identifies an HSF-independent mechanism that links nascent-protein ubiquitination to transcriptional downregulation during heat shock, with potential ramifications in neurodegenerative diseases.
2019-02-07 | GSE112379 | GEO
Project description:Vibrio cholerae, the cause of cholera, can grow in a variety of environments outside of human hosts. During infection, the pathogen must adapt to significant environmental alterations, including the elevated temperature of the human gastrointestinal tract. σ32, an alternative sigma factor encoded by rpoH, activates transcription of genes involved in the heat-shock response in several bacterial species. We defined the V. cholerae RpoH regulon by comparing the whole genome transcription profiles of the wild-type and rpoH mutant strains after a temperature up-shift. Most of the V. cholerae genes expressed in an RpoH-dependent manner after heat-shock encode proteins that influence protein fate, such as proteases and chaperones, or are of unknown function. Keywords: heat-shock response, rpoH
2007-01-03 | GSE6097 | GEO
Project description:During heat stress cyto-protective genes including heat shock proteins are transcriptionally up-regulated and post-transcriptional splicing is inhibited. In contrast, co-transcriptional mRNA-splicing is maintained. These factors closely resemble the proteotoxic stress response during tumor development. The bromodomain protein BRD4 has been identified as an integral member of the oxidative stress as well as of the inflammatory response. Furthermore, there is evidence for BRD4's role in splicing regulation; Using RNA-Seq analyses we indeed found a significant increase in splicing inhibition, in particular intron retentions, during heat treatment in BRD4-deficient cells, but not under normal conditions. Subsequent experiments revealed that heat stress leads to the recruitment of BRD4 to nuclear stress bodies, to the interaction with the heat shock factor 1 (HSF1) and to the transcriptional up-regulation of non-coding Sat III RNA transcripts. These findings implicate BRD4 as a central regulator of splicing during heat stress. Since BRD4 is a potent target for anti-cancer therapies, our data linking BRD4 to the splicing machinery and the heat stress response - give additional insight into the mode of action of BRD4 inhibitors. WI38 cells have been treated by heatshock and anti BRD4 siRNA and combination.
2016-09-07 | E-GEOD-73471 | biostudies-arrayexpress
Project description:During heat stress cyto-protective genes including heat shock proteins are transcriptionally up-regulated and post-transcriptional splicing is inhibited. In contrast, co-transcriptional mRNA-splicing is maintained. These factors closely resemble the proteotoxic stress response during tumor development. The bromodomain protein BRD4 has been identified as an integral member of the oxidative stress as well as of the inflammatory response. Furthermore, there is evidence for BRD4's role in splicing regulation; Using RNA-Seq analyses we indeed found a significant increase in splicing inhibition, in particular intron retentions, during heat treatment in BRD4-deficient cells, but not under normal conditions. Subsequent experiments revealed that heat stress leads to the recruitment of BRD4 to nuclear stress bodies, to the interaction with the heat shock factor 1 (HSF1) and to the transcriptional up-regulation of non-coding Sat III RNA transcripts. These findings implicate BRD4 as a central regulator of splicing during heat stress. Since BRD4 is a potent target for anti-cancer therapies, our data linking BRD4 to the splicing machinery and the heat stress response - give additional insight into the mode of action of BRD4 inhibitors.
2016-09-07 | GSE73471 | GEO