Transcriptome-wide RNA and genome-wide DNA G-Quadruplex mediates alternative transcripts
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ABSTRACT:
ORGANISM(S): Rattus norvegicus Homo sapiens
PROVIDER: GSE116461 | GEO | 2025/02/01
REPOSITORIES: GEO
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Project description:A375 and HT1080 cells are treated with G-quadruplex ligands PDS or PhenDC3 following genome-wide shRNA knockdown. This enables the identification of genes that when silenced, specifically compromises cell growth in the presence of the ligand. First, a pilot screen was performed to determine a ligand concentration and experimental duration that caused ligand-specific, significant changes in shRNA levels. Second, a genome-wide screen was performed to globally evaluate G4-ligand synthetic lethal interactions. Third, to corroborate the G4-sensitisers uncovered in the genome-wide screen, a focussed screen was performed with a custom shRNA pool.
2019-06-22 | E-MTAB-6367 | biostudies-arrayexpress
Project description:We systematically analyzed the alterations in mRNA transcriptome evoked by knockdown of YY1 with or without pyridostatin (PDS) treatment. Statistical analysis showed a strong correlation between PDS-regulated and YY1-regulated genes (Pearson r > 0.67), underscoring the role of YY1-G4 structure interaction in YY1-mediated gene regulation. Moreover, the RNA-Seq results revealed that YY1 can positively or negatively regulate the expression of genes through its interaction with G4 structures.
2020-08-27 | GSE142075 | GEO
Project description:Transcriptome-wide RNA and genome-wide DNA G-Quadruplex mediates alternative transcripts
| PRJNA478594 | ENA
Project description:A great deal of attention is being paid to strategies seeking to uncover the biology of the four-stranded nucleic acid structure G-quadruplex (G4) via their stabilization in cells with G4-specific ligands. The conventional definition of chemical biology implies that a complete assessment of G4 biology can only be achieved by implementing a complementary approach involving destabilization of cellular G4s by ad hoc molecular effectors. We report here on an unprecedented comparison of the cellular consequences of G4 chemical stabilization by pyridostatin (PDS) and destabilization by phenylpyrrolocytosine (PhpC) at both transcriptome- and proteome-wide scales in patient-derived primary human astrocytes. Our results show that the stabilization of G4s by PDS triggers the dysregulation of many cellular circuitries, the most drastic effects originating in downregulation of 354 transcripts and 158 proteins primarily involved in RNA transactions. In contrast, destabilization of G4s by PhpC modulates the G4 landscapes in a far more focused manner with upregulation of 295 proteins, mostly involved in RNA transactions as well, thus mirroring the effects of PDS. Our study is the first of its kind to report the extent of G4-associated cellular circuitries in human cells by systematically pitting the effect of G4 stabilization against destabilization in a direct and unbiased manner.
2025-01-29 | GSE279752 | GEO
Project description:G-quadruplex (G4) structure is an alternative conformation of the double helical structure of B-form DNA arisen in guanine-rich sequences . The formation of G4 structures can influence chromatin architecture and many fundamental biology processes, such as DNA replication and gene regulation . We present G4-miner, a genome-wide approach to directly identify G4 structures from ordinary sequencing data. G4-miner inspects sequencing quality in whole genome, seizes unexpected fluctuations in local, and ascribes some of the quality fluctuations to the unstable formation of G4. We identified 736,689 G4 structures within human genome, in which 44.9% of all predicted canonical G4-froming sequences were contained.
2020-10-10 | GSE159307 | GEO
Project description:G-quadruplex structure (G4) is a type of DNA secondary structure that widely exists in the genomes of many organisms. G4s are believed to participate in multiple biological processes. Acyl- CoA binding protein (ACBP), a ubiquitously expressed and highly conserved protein in eukaryotic cells, plays important roles in lipid metabolism by transporting and protecting acyl-CoA esters. Here, we report the functional identification of a G4 in the promoter of the ACBP gene in silkworm and human cancer cells. We found that G4 exists as a conserved element in the promoters of ACBP genes in invertebrates and vertebrates. The BmACBP G4 bound with G4-binding protein LARK regulated BmACBP transcription, which was blocked by the G4 stabilizer pyridostatin (PDS) and G4 antisense oligonucleotides. PDS treatment with 5 th instar silkworm larvae decreased the BmACBP expression and triacylglycerides (TAG) level, resulting in reductions in fat body mass, body size and weight and growth and metamorphic rates. PDS treatment and knocking out of the HsACBP G4 in human hepatic adenocarcinoma HepG2 cells inhibited the expression of HsACBP and decreased the TAG level and cell proliferation. Altogether, our findings suggest that G4 of the ACBP genes is involved in regulation of lipid metabolism processes in invertebrates and vertebrates.
2022-05-04 | GSE201939 | GEO
Project description:RNA structures are of crucial importance for biological function and gene regulation. Guanine (G)-rich sequences in RNA can assemble to form RNA G-quadruplex (rG4) structures; specific rG4s have been shown to regulate gene expression, and are associated with human diseases. However, no transcriptome-wide method has been reported to map rG4s, limiting our understanding of the rG4 structure and its relationship with function and regulation. Here we introduce a transcriptome-wide rG4 profiling method, rG4-Seq, in which the rG4-mediated reverse transcriptase stalling is read out by next-generation sequencing at nucleotide resolution. We apply this method to human RNA and report the first global map of rG4 structures for any organism. Our analysis identifies over 3,000 rG4s, and increases to over 11,000 upon addition of a rG4 stabilizing ligand Pyridostatin (PDS). Notably, we discover that besides canonical rG4s, many rG4s are non-canonical with novel structural features such as long-loops, bulges, and 2-quartet. We also find that rG4 formation is associated with its stability, Cytosine (C)-content, and the stability of alternative RNA structures. Our data reveals that rG4s can be found in messenger RNAs (mRNAs) and long intergenic noncoding RNAs (lincRNAs). In mRNAs, rG4s are enriched in untranslated regions, and are significantly correlated with microRNA target sites and polyadenylation signals. Remarkably, we found that majority of our in vitro identified rG4s can change the in silico predicted RNA structure to uncover alternative RNA conformation.. Futhermore, the rG4s that have analogues in many ortholog genes across different species show a preferential association with RNA processing and stability. rG4-seq is a broadly applicable method that enables the RNA G4 structurome and its biological roles to be interrogated and can be readily applied in other organisms on a transcriptome-wide scale. 12 samples, 150 bp single-ended RNA-Seq libraries from cell extracts after performing RTS reaction in different buffers (Li, K and K+PDS rich buffer). Each of the 3 conditions has 4 libraries from independent biological replicates.
2016-08-10 | E-GEOD-77282 | biostudies-arrayexpress
Project description:G-quadruplex (G4) is non-canonical nucleic acid structure involved in a plethora of fundamental biological processes. In past decades, it has been studied as a promising pharmaceutical target for anticancer therapy. However, no G4-targeting agent has shown significant clinical effects up to date. Pyridostatin (PDS), a well-known G4 binder, can induce double-stranded DNA breaks and genome instability. We have recently shown that Pyridostatin (Pyridostatin) and other G4 binders can trigger micronuclei formation in cancer cells at non-cytotoxic concentrations. As micronuclei can play a crucial role in linking genome instability to innate immunity, we have here wondered whether G4 binders can induce immune gene activation in human MCF-7 breast cancer cells.
2021-07-14 | GSE161418 | GEO
Project description:DNA sequences of high guanine (G) content have the potential to fold into G quadruplex (G4) structures. DNA G4 is known to play important roles in various cellular processes including DNA replication, transcriptional regulation, and maintenance of genomic integrity. A more complete understanding about the biological functions of G4 DNA requires the investigation about how these structures are recognized by cellular proteins. Here, we conducted exhaustive quantitative proteomic experiments to profile the interaction proteomes of three well-defined G4 structures derived from the human telomere and the promoters of cMYC and cKIT genes. Our results led to the identification of a number of candidate G4-interacting proteins; some were previously reported, e.g., FUS, TOP1, and PARP1, and many others were discovered here for the first time. These included three proteins that can bind to all three DNA G4 structures and many proteins that can bind specifically to selected DNA G4 structure(s). We also validated that GRSF1 can bind directly and selectively toward G4 DNA structure derived from the cMYC promoter. Taken together, we uncovered a number of cellular proteins that exhibit general and selective recognitions of G4 folding patterns, which underscore the complexity of G4 DNA in biology and the importance in understanding fully the G4-interaction proteome.
2021-09-29 | PXD026794 | Pride
Project description:High-order chromatin organization plays an important role in biological processes and disease development. Previous studies revealed a widespread occurrence of guanine quadruplex (G4) structures in the human genome, with enrichment in gene regulatory regions, especially in promoters. However, it remains unclear if G4 structures contribute to RNA polymerase II (RNAPII)-mediated long-range DNA interactions and transcription activity. In this study, we conducted an intuitive overlapping analysis of previously published data of RNAPII ChIA-PET (chromatin interaction analysis with paired-end tag) and BG4 ChIP-seq (chromatin immunoprecipitation followed by sequencing with the use of a G4 structure-specific antibody). We observed a strong positive correlation between RNAPII-mediated DNA loops and G4 structures in chromatin. Additionally, our RNAPII HiChIP-seq (in situ Hi-C followed by ChIP-seq) results showed that treatment of HepG2 cells with pyridostatin (PDS), a small-molecule G4-stabilization ligand, could diminish RNAPII-linked long-range DNA contacts, with more pronounced decreases being observed for those contacts involving G4 structure loci.
2023-09-13 | GSE222206 | GEO