The 3’ Untranslated Region (3’UTR) Coding Sequence of PHO84, Rather Than the Antisense RNA, Promotes Gene Repression
Ontology highlight
ABSTRACT:
ORGANISM(S): Saccharomyces cerevisiae
PROVIDER: GSE227252 | GEO | 2023/08/17
REPOSITORIES: GEO
Similar Datasets
Project description:VEGF165 is one of the key regulators of tumor development. Using HCT116 cells transfected with full-length vegf mRNA, full-length vegf mRNA with mutations of H9D and L14E, mutated vegf mRNAs lacking untranslated regions (UTRs), and 5’UTR mutated between nt 591 and nt 746, we found that vegf 5’UTR resided an anti-apoptotic activity against chemotherapy independently of VEGF165. We next established HCT116 clones stably expressing vegf 5’UTR or the mutated vegf 5’UTR. The cells expressing 5’UTR, but not the mutated UTR, showed the drug-resistant phenotype, anchorage-independent growth, and rapid tumor growth when implanted in athymic nude mice. Microarray and real-time PCR showed that the vegf 5’UTR-expressing tumors up-regulated anti-apoptotic genes including mia and down-regulated pro-apoptotic genes including fas, pdcd1, nrg1, and bax. Microarray analysis also revealed specific down-regulation of IFN-inducible genes (43 genes) in the growing tumors. HCT116 cells stably transcribing vegf 5’UTR decreased STAT1 expression and IFN alpha-STAT1 pathway. In addition to 5-fluorouracil treatment, the vegf 5’UTR-expressing tumors did not respond to IFN alpha therapy at all. This novel tumor-promoting function in the vegf 5’UTR may partly explain the insufficiency of the VEGF-VEGFR strategies and suggest a vegf-targeted silencing strategy as a more effective anti-tumor therapy. Keywords: genetic modification
2008-04-04 | GSE8888 | GEO
Project description: Not available
| S-EPMC7476403 | biostudies-literature
Project description:The functional consequences of genetic variants within 5’ untranslated regions (UTRs) on a genome-wide scale are poorly understood in disease. We developed a high-throughput multi-layer massively parallel sequencing-based method called PLUMAGE (Pooled full-length UTR Multiplex Assay on Gene Expression) to quantify the molecular consequences of somatic 5’ UTR mutations found across 229 prostate cancer patients with localized to metastatic disease. We show that 5’ UTR mutations can control both transcript levels and mRNA translation rates through the creation of new DNA binding elements or RNA-based cis-regulatory motifs. We also discover that single point mutations can simultaneously impact both transcript levels and mRNA translation of the same gene. Using gene editing technology, we validate that a single point mutation in the oncogenic CKS2 5’ UTR can increase mRNA specific translation. Turning to a molecular pathway critical for cancer, we provide evidence that functional 5’ UTR mutations in the MAP kinase signaling pathway can upregulate pathway-specific gene expression and are associated with distinct clinical outcomes. Our study reveals the diverse mechanisms by which the mutational landscape of 5’ UTRs can co-opt multiple levels of gene expression and demonstrates that single nucleotide alternations within leader sequences are functional in cancer.
2021-05-17 | GSE171729 | GEO
Project description:Mature messenger RNAs (mRNAs) consist of coding sequence (CDS) and 5’ and 3’ untranslated regions, typically expected to show similar abundance within a given neuron. Examining mRNA from defined neurons we unexpectedly show extremely common unbalanced expression of cognate 3’ UTR and CDS sequences, observing many genes with high UTR relative to CDS, and others with high CDS to UTR. By in situ hybridization 19 of 19 genes examined show a broad range of UTR to CDS expression ratios in different neurons and other tissues. These ratios may be spatially graded or change with developmental age, but are consistent across animals. Further, for two genes examined, a UTR to CDS ratio above a particular threshold in any given neuron correlated with reduced or undetectable protein expression. Our findings raise questions about the role of isolated UTR sequences in regulation of protein expression, and highlight the importance of separately examining UTR and CDS sequences in gene expression analyses.
2016-03-04 | GSE75596 | GEO
Project description: Not available
| S-EPMC2638016 | biostudies-literature
Project description:Analysis of MCF-7 cells following six2 or CYP4Z1 3'UTR or CYP4Z2P 3'UTR overexpression. Overexpression of six2 or CYP4Z1 3'UTR or CYP4Z2P 3'UTR positively regulates the abundance of embryonic stem cell function. Results provide insight into the role of six2 mediated-regulation on the ceRNA network between CYP4Z1 and pseudogene CYP4Z2P in breast cancer stemness.
2019-03-10 | GSE116984 | GEO
Project description:The functional consequences of cancer patient-derived genetic variants within the 5’ untranslated regions (UTRs) on a genome-wide scale and their effects on mRNA transcript and translation levels are poorly understood. To systematically interrogate the mutational landscape of 5’ UTRs across cancer patients with localized to metastatic disease, we analyzed the genomes of 226 prostate cancer patients and observed thousands of mutations, many of which impact known cis-regulatory elements. We developed a high-throughput multi-layer massively parallel sequencing-based method called PLUMAGE (Pooled full-length UTR Multiplex Assay on Gene Expression) to simultaneously quantify the effects of 545 5’ UTR somatic mutations across recurrently mutated or cancer-related genes from our patient cohort. Our method enabled unprecedented insights into how 5’ UTR mutations can control multiple levels of gene expression simultaneously. In particular, we identified 190 mutations that significantly altered 5’ UTR function, either by creating new DNA binding elements, disrupting known translation regulatory motifs, or simultaneously impacting both transcript levels and mRNA translation. Furthermore, we also determined that 5’ UTR mutations to the MAP kinase signaling pathway are significantly associated with early metastasis. This study is the first to comprehensively interrogate the functional 5’ UTR mutational landscape of a human cancer revealing the importance of untranslated regions in regulating multiple levels of oncogenic gene expression and provides a high-throughput functional genomics solution applicable to many genetically driven diseases.
2021-05-17 | GSE149487 | GEO
Project description:Processing of 3’ untranslated region (3’-UTR) of precursor messenger RNAs (pre-mRNA) is a fundamental step in mRNA maturation, where the mRNA transcript is cleaved at a specific site, located downstream the open reading frame of the encoded gene. The position of the cleavage site is determined by cis-acting RNA sequence elements, which are recognized with high specificity by large 3’ end processing multiprotein complexes. Two main categories of metazoan 3’ pre-mRNA processing have been identified so far, describing elaboration of either canonical mRNAs – occurring during all phases of the cell cycle and containing a characteristic Poly-Adenylation Signal (PAS) element – or histone mRNAs – prevalently occurring during the S phase and containing a Histone Downstream Element (HDE). In this work, we isolate both human endogenous canonical and histone 3’ pre-mRNA processing complexes from human nuclear extracts by using a pre-mRNA containing the 3’UTR sequence of replication-dependent histone H2A.2. This H2A.2 pre-mRNA (H2A_4m), containing both an HDE sequence and a PAS element in a native overlaid position, was modified with a 5’ photocleavable biotin tag, and with modification of few bases to allow complex assembly and purification by affinity chromatography on streptavidin-agarose beads, elution by UV irradiation and subsequent mass spectrometric identification of bound 3’ mRNA processing factors.
2022-12-09 | PXD034984 | Pride
Project description:The functional consequences of cancer patient-derived genetic variants within the 5’ untranslated regions (UTRs) on a genome-wide scale and their effects on mRNA transcript and translation levels are poorly understood. To systematically interrogate the mutational landscape of 5’ UTRs across cancer patients with localized to metastatic disease, we analyzed the genomes of 226 prostate cancer patients and observed thousands of mutations, many of which impact known cis-regulatory elements. We developed a high-throughput multi-layer massively parallel sequencing-based method called PLUMAGE (Pooled full-length UTR Multiplex Assay on Gene Expression) to simultaneously quantify the effects of 545 5’ UTR somatic mutations across recurrently mutated or cancer-related genes from our patient cohort. Our method enabled unprecedented insights into how 5’ UTR mutations can control multiple levels of gene expression simultaneously. In particular, we identified 190 mutations that significantly altered 5’ UTR function, either by creating new DNA binding elements, disrupting known translation regulatory motifs, or simultaneously impacting both transcript levels and mRNA translation. Furthermore, we also determined that 5’ UTR mutations to the MAP kinase signaling pathway are significantly associated with early metastasis. This study is the first to comprehensively interrogate the functional 5’ UTR mutational landscape of a human cancer revealing the importance of untranslated regions in regulating multiple levels of oncogenic gene expression and provides a high-throughput functional genomics solution applicable to many genetically driven diseases.
2021-05-20 | GSE174787 | GEO
Project description:The functional consequences of cancer patient-derived genetic variants within the 5’ untranslated regions (UTRs) on a genome-wide scale and their effects on mRNA transcript and translation levels are poorly understood. To systematically interrogate the mutational landscape of 5’ UTRs across cancer patients with localized to metastatic disease, we analyzed the genomes of 226 prostate cancer patients and observed thousands of mutations, many of which impact known cis-regulatory elements. We developed a high-throughput multi-layer massively parallel sequencing-based method called PLUMAGE (Pooled full-length UTR Multiplex Assay on Gene Expression) to simultaneously quantify the effects of 545 5’ UTR somatic mutations across recurrently mutated or cancer-related genes from our patient cohort. Our method enabled unprecedented insights into how 5’ UTR mutations can control multiple levels of gene expression simultaneously. In particular, we identified 190 mutations that significantly altered 5’ UTR function, either by creating new DNA binding elements, disrupting known translation regulatory motifs, or simultaneously impacting both transcript levels and mRNA translation. Furthermore, we also determined that 5’ UTR mutations to the MAP kinase signaling pathway are significantly associated with early metastasis. This study is the first to comprehensively interrogate the functional 5’ UTR mutational landscape of a human cancer revealing the importance of untranslated regions in regulating multiple levels of oncogenic gene expression and provides a high-throughput functional genomics solution applicable to many genetically driven diseases.
2021-05-17 | GSE130465 | GEO