GEO accession GSE237235 is currently private and is scheduled to be released on Dec 01, 2025.
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA994447 | ENA |
REPOSITORIES: ENA
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Project description:Pcf11 is a transcriptional termination factor that interferes with cell survival and mRNA 3′-end processing. However, the mechanism by which Pcf11 regulates transcriptional termination and the molecular basis of its interaction with the terminator remain unclear. Here, we performed gene expression profile, binding pattern, and RNA-binding motif studies on Pcf11. We used in vivo CLIP-seq to map thousands of Pcf11 binding sites in Saccharomyces cerevisiae and revealed the RNA-binding motifs of Pcf11 in the 3'-UTR region.
2025-12-01 | GSE237235 | GEO
Project description:N6,2’-O-dimethyladenosine (m6Am) is an abundant mRNA modification that impacts multiple diseases but its function remains controversial since the m6Am reader is unknown. Using quantitative proteomics, we identified transcriptional terminator PCF11 as a m6Am-specific reader. Direct quantification of mature versus nascent RNAs reveals m6Am does not regulate mRNA stability but promotes nascent transcription. Mechanistically, m6Am functions by sequestering PCF11 away from proximal RNA Pol II. This suppresses PCF11 from dissociating Pol II near transcription start sites, thereby promoting full-length transcription of m6Am-modified RNAs. m6Am’s unique relationship with PCF11 means m6Am function is enhanced when PCF11 is reduced, which occurs during all-trans-retinoic-acid (ATRA) induced neuroblastoma-differentiation therapy. Here, m6Am promotes expression of ATF3, a repressor of the neuroblastoma biomarker MYCN. Depleting m6Am suppresses MYCN-repression in ATRA-treated neuroblastoma and maintains their tumour stem-like properties. Collectively, we characterize m6Am as an anti-terminator RNA modification that suppresses premature termination and modulates neuroblastoma therapeutic response.
2024-10-31 | GSE266116 | GEO
Project description:Genes with different sizes have distinct expression patterns and functions. Here we show that the 3' end processing PCF11 modulates gene expression according to gene size. Gene density and polyA site strength, but not orientation between neighboring genes, impact short gene regulation by PCF11. In contrast, long gene modulation involves intronic polyadenylation (IPA), which is widespread in large introns. Downregulation of PCF11, which takes place in cell differentiation, contributes to short and long gene expressions with functions related to cell proliferation, cell morphology, adhesion, and migration. Mild, exogenous upregulation of PCF11 perturbs the gene expression program in cell differentiation. Further, PCF11 is auto-regulated through a highly conserved IPA site, the removal of which leads to PCF11 overexpression and global activation of proximal PASs sites. Together, our data indicate that PCF11 level impacts gene expression based on size and its autoregulation maintains homeostasis of PAS usage in the cell.
2019-02-12 | GSE115232 | GEO
Project description:RNA-seq expression analysis of Pcf11 mutations Pcf11-13 and Pcf11-DNL
| PRJNA785635 | ENA
Project description:High Throughput bulk-sample RNA-sequencing expression data, was collected for triplicate samples of two distinct mutations of Pcf11 and a matched wildtype w303 samples under standard growth conditions. The overall goal was quantification of expression abundance and pre-mRNA processing changes in response to these mutations.
2023-11-01 | GSE190051 | GEO
Project description:The 3' end of a gene, often called a terminator, modulates mRNA stability, localization, translation, and polyadenylation. Here, we adapted Plant STARR-seq, a massively parallel reporter assay, to measure the activity of over 50,000 terminators from the plants Arabidopsis thaliana and Zea mays. We characterize thousands of plant terminators, including many that outperform bacterial terminators commonly used in plants. Terminator activity is species-specific, differing in tobacco leaf and maize protoplast assays. While recapitulating known biology, our results reveal the relative contributions of polyadenylation motifs to terminator strength. We built a computational model to predict terminator strength and used it to conduct in silico evolution that generated optimized synthetic terminators. Additionally, we discover alternative polyadenylation sites across tens of thousands of terminators; however, the strongest terminators tend to have a dominant cleavage site. Our results establish features of plant terminator function and identify strong naturally occurring and synthetic terminators.
| S-EPMC11245536 | biostudies-literature
Project description:The pervasive nature of RNA polymerase II (Pol II) transcription requires efficient termination. A key player in this process is the cleavage and polyadenylation (CPA) factor PCF11, which directly binds to the Pol II C-terminal domain and dismantles elongating Pol II from DNA in vitro. We demonstrate that PCF11-mediated termination is essential for vertebrate development. A range of genomic analyses, including: mNET-seq, 3’ mRNA-seq, chromatin RNA-seq and ChIP-seq, reveals that PCF11 enhances transcription termination and stimulates early polyadenylation genome-wide. PCF11 binds preferentially between closely spaced genes, where it prevents transcriptional interference and downstream gene silencing. Notably, PCF11 is sub-stoichiometric to the CPA complex. Low levels of PCF11 are maintained by an auto-regulatory mechanism involving premature termination of its own transcript, and are important for normal development. Both in human cell culture and during zebrafish development, PCF11 selectively attenuates the expression of other transcriptional regulators by premature CPA and termination.
2019-02-28 | GSE127256 | GEO
Project description:The pervasive nature of RNA polymerase II (Pol II) transcription requires efficient termination. A key player in this process is the cleavage and polyadenylation (CPA) factor PCF11, which directly binds to the Pol II C-terminal domain and dismantles elongating Pol II from DNA in vitro. We demonstrate that PCF11-mediated termination is essential for vertebrate development. A range of genomic analyses, including: mNET-seq, 3’ mRNA-seq, chromatin RNA-seq and ChIP-seq, reveals that PCF11 enhances transcription termination and stimulates early polyadenylation genome-wide. PCF11 binds preferentially between closely spaced genes, where it prevents transcriptional interference and downstream gene silencing. Notably, PCF11 is sub-stoichiometric to the CPA complex. Low levels of PCF11 are maintained by an auto-regulatory mechanism involving premature termination of its own transcript, and are important for normal development. Both in human cell culture and during zebrafish development, PCF11 selectively attenuates the expression of other transcriptional regulators by premature CPA and termination.
2019-02-25 | GSE123104 | GEO
Project description:The pervasive nature of RNA polymerase II (Pol II) transcription requires efficient termination. A key player in this process is the cleavage and polyadenylation (CPA) factor PCF11, which directly binds to the Pol II C-terminal domain and dismantles elongating Pol II from DNA in vitro. We demonstrate that PCF11-mediated termination is essential for vertebrate development. A range of genomic analyses, including: mNET-seq, 3’ mRNA-seq, chromatin RNA-seq and ChIP-seq, reveals that PCF11 enhances transcription termination and stimulates early polyadenylation genome-wide. PCF11 binds preferentially between closely spaced genes, where it prevents transcriptional interference and downstream gene silencing. Notably, PCF11 is sub-stoichiometric to the CPA complex. Low levels of PCF11 are maintained by an auto-regulatory mechanism involving premature termination of its own transcript, and are important for normal development. Both in human cell culture and during zebrafish development, PCF11 selectively attenuates the expression of other transcriptional regulators by premature CPA and termination.
2019-02-25 | GSE124556 | GEO
Project description:The pervasive nature of RNA polymerase II (Pol II) transcription requires efficient termination. A key player in this process is the cleavage and polyadenylation (CPA) factor PCF11, which directly binds to the Pol II C-terminal domain and dismantles elongating Pol II from DNA in vitro. We demonstrate that PCF11-mediated termination is essential for vertebrate development. A range of genomic analyses, including: mNET-seq, 3’ mRNA-seq, chromatin RNA-seq and ChIP-seq, reveals that PCF11 enhances transcription termination and stimulates early polyadenylation genome-wide. PCF11 binds preferentially between closely spaced genes, where it prevents transcriptional interference and downstream gene silencing. Notably, PCF11 is sub-stoichiometric to the CPA complex. Low levels of PCF11 are maintained by an auto-regulatory mechanism involving premature termination of its own transcript, and are important for normal development. Both in human cell culture and during zebrafish development, PCF11 selectively attenuates the expression of other transcriptional regulators by premature CPA and termination.
2019-02-25 | GSE124555 | GEO