Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

TCERG1 regulates alternative splicing of Bcl-x gene by modulating the rate of RNAPII transcription

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE33716 | GEO | 2012/01/12

SECONDARY ACCESSION(S): PRJNA148459

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

TCERG1 regulates alternative splicing of Bcl-x gene by modulating the rate of RNAPII transcription

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

Analysis of the implication of the DBIRD complex (DBC1 and ZNF326/ZIRD) in gene expression and alternative splicing

Project description:Alternative mRNA splicing is the main reason vast mammalian proteomic complexity can be achieved with a limited number of genes. Splicing is physically and functionally coupled to transcription and the rate of transcript elongation has a profound effect on splicing. As the nascent pre-mRNA emerges from transcribing RNA polymerase II (RNAPII), it is assembled into a messenger ribonucleoprotein (mRNP) particle that represents its functional form, and the composition of which determines the fate of the mature transcript4. However, factors that connect the transcribing polymerase with the mRNP particle and help integrate transcript elongation with mRNA splicing remain obscure. Here, we characterized the interactome of chromatin-associated mRNP particles and thereby identified Deleted in Breast Cancer 1 (DBC1) and a protein we named ZIRD. These proteins are subunits of a novel protein complex, named DBIRD, which binds directly to RNAPII. DBIRD regulates alternative splicing of a large set of exons embedded in A/T-rich DNA, and is present at the affected exons. RNAi-mediated DBIRD depletion results in region-specific decreases in transcript elongation, particularly across areas encompassing affected exons. These data indicate that DBIRD complex acts at the interface between mRNP particles and RNAPII, integrating transcript elongation with regulation of alternative splicing. HEK 293 cells were transfected with CTR-, DBC1- and ZIRD (ZNF326)- specific stealth siRNAs. Total RNAs from three independent experiments were extracted after 48 hours. All conditions were analyzed in triplicate.

2012-03-20 | E-GEOD-35480 | biostudies-arrayexpress

Regulation of pre-mRNA splicing by m6A through the low-complexity protein hnRNPG and co-transcriptional pausing

Project description:Co-transcriptional processing of nascent transcripts is coupled with transcription through the carboxy-terminal domain (CTD) of RNA polymerase II (RNAPII). The mRNA modification N6-methyladenosine (m6A) occurs co-transcriptionally and impacts pre-mRNA processing. How alternative splicing of pre-mRNA is co-transcriptionally regulated in an m6A-dependent manner is not well understood. Furthermore, splicing regulation through RNAPII pausing has been frequently suggested but the underlying control mechanism remains unclear. Here, we show that the m6A reader protein hnRNPG directly binds to the phosphorylated CTD of RNAPII using Arg-Gly-Gly (RGG) motifs in its low-complexity region. This RGG-phospho-CTD interaction and nascent RNA binding by hnRNPG enables its co-transcriptional association with RNAPII, resulting in transcriptome-wide regulation of alternative splicing and transcript abundance. m6A sites near exon splice sites in nascent mRNA further modulate hnRNPG binding and exon splicing. Exon inclusion is associated with RNAPII pausing downstream of the m6A site. Our results reveal an integrated nuclear mechanism of m6A-mediated gene regulation, in which an m6A reader protein regulates gene expression by using RGG motifs to co-transcriptionally interact with both RNAPII and m6A-modified nascent pre-mRNA, while the interplay between hnRNPG binding and RNAPII pausing modulates alternative splicing regulation.

2019-09-05 | GSE114311 | GEO

Determining the impact of alternative splicing events on transcriptome dynamics

Project description:Background The complete sequencing of the human genome and its subsequent analysis revealed a predominant role for alternative splicing in the generation of proteome diversity. Splice switching oligonucleotides (SSOs) are a powerful and specific tool to experimentally control alternative splicing of endogenous messenger RNAs in living cells. SSOs also have therapeutic potential to treat diseases that are caused by aberrant splicing. The assignment of biological roles to alternative splicing events of currently unknown function promises to provide a largely untapped source of potential new therapeutic targets. Here we have developed a protocol that combines high sensitivity microarrays with the transfection of SSOs to monitor global changes in gene expression downstream of alternate, endogenous splice events. Findings When applied to a well-characterized splicing event in the Bcl-x gene, the application of high sensitivity microarrays revealed a link between the induction of the Bcl-xS isoform and the repression of genes involved in protein synthesis. Conclusions The strategy introduced herein provides a useful approach to define the biological impact of any given alternative splicing event on global gene expression patterns. Furthermore, our data provide the first link between Bcl-xS expression and the repression of ribosomal protein gene expression. Biological triplicates, 2 conditions: control oligonucleotide, Bcl-x oligonucleotide

2008-10-02 | E-GEOD-9851 | biostudies-arrayexpress

Slow transcriptional elongation causes embryonic lethality and perturbs kinetic coupling of long neural genes [RNA-seq]

Project description:The rate of RNA Polymerase II (RNAPII) elongation has an important role in the control of Alternative splicing (AS); however, the in vivo consequences of an altered elongation rate are unknown. Here, we generated mouse embryonic stem cells (ESCs) knocked-in for a slow elongating form of RNAPII. We show that a reduced transcriptional elongation rate results in early embryonic lethality in mice and impairs the differentiation of ESCs into the neural lineage. This is accompanied by changes in splicing and in gene expression in ESCs and along the pathway of neuronal differentiation. In particular, we found a crucial role for RNAPII elongation rate in transcription and splicing of long neuronal genes involved in synapse signaling. The impact of the kinetic coupling of RNAPII elongation rate with AS is more predominant in ESC-differentiated neurons than in pluripotent cells. Our results demonstrate the requirement for an appropriate transcriptional elongation rate to ensure proper gene expression and to regulate AS during development.

2019-04-15 | GSE125413 | GEO

Slow transcriptional elongation causes embryonic lethality and perturbs kinetic coupling of long neural genes [4sURDB-Seq]

2019-04-15 | GSE127740 | GEO

Determining the impact of alternative splicing events on transcriptome dynamics

2008-10-02 | GSE9851 | GEO

Analysis of the implication of the DBIRD complex (DBC1 and ZNF326/ZIRD) in gene expression and alternative splicing

2012-03-20 | GSE35480 | GEO

The chromatin remodeler Ino80 mediates alternative RNAPII pausing site determination

Project description:Promoter-proximal pausing of RNAPII is a critical step in early transcription elongation to precisely regulate gene expression. Here, we observed evidence of promoter-proximal pausing like distributions of RNAPII in S. cerevisiae. We find that Ino80p loss caused the transition of RNAPII pausing to the alternative pausing site at which is tightly associated with the +1 nucleosome. These Ino80p dependent genes showed better nucleosome positioning around the main pausing site which suggested the regulation of RNAPII pausing by Ino80p in a nucleosome context-dependent manner. Furthermore, we examined the similar INO80 dependent RNAPII pausing site determination in mESCs. Altogether, we hypothesize a highly conserved role of the chromatin remodeling Ino80 complex in controlling the early RNAPII elongation to establish intact pausing in various organisms, from budding yeast to mouse.

2021-08-20 | GSE158622 | GEO

NETSeq Analysis of the Effect of PARP-1 Knockdown in Drosophila Melanogaster

Project description:Multiple roles for PARP1 have been elucidated including DNA damage repair, metabolic regulation, and cell cycle control. PARP1 also has an effect on chromatin structure, but this factor has not been well studied. Here, we strive to elucidate the effect of PARP1-mediated chromatin changes, specifically in the context of transcription and alternative splicing. Chromatin structure affects any process that occurs on the DNA, including transcription and splicing. Therefore, if PARP1 has an effect on chromatin structure, it will cause downstream changes in transcription and splicing. We investigated PARP1’s connection to splicing not only by evaluating splicing decisions, but also by studying its effect on splicing factors. We found that PARP1 has a multifaceted role in these processes. PARP1 presence influences splicing decisions by altering nucleosome deposition and histone post-translational modifications at exon-intron boundaries. Additionally, PARP1 occupancy modifies transcriptional elongation by hindering the rate of RNAPII movement. In this study, we show that through changes in chromatin structure, PARP1 is able to modify transcriptional elongation rates as well as alternative splicing decisions.

2021-08-06 | GSE118266 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data