Global analyses of RNA G-quadruplexes
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ABSTRACT:
PROVIDER: PRJNA326510 | ENA |
REPOSITORIES: ENA
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Project description:In vitro, some RNAs can form stable four-stranded structures known as G-quadruplexes. Although RNA G-quadruplex structures have been implicated in post-transcriptional gene regulation and diseases, direct evidence for quadruplex formation in cells has been lacking. Here, we developed a suite of methods that identify RNAs with quadruplex-forming ability and measure their folding state in living cells. Applying these methods to mammalian cell lines, the budding yeast S. cerevisiae and several bacteria, we characterized the folding landscapes of RNA G-quadruplexes in these species.
2016-09-24 | GSE83617 | GEO
Project description:G-quadruplexes (G4s) are noncanonical DNA secondary structures formed through the self-association of guanines. They are distributed genome-widely and participate in multiple biological processes including gene transcription, and quadruplex-targeted ligands serve as potential therapeutic agents for DNA-targeted therapies. However, the roles of G-quadruplexes in transcriptional regulation remains elusive. Here, we establish a sensitive G4-CUT&Tag method for genome-wide profiling of native G-quadruplexes with high resolution and specificity. We find that native G-quadruplex signals are cell-type specific and are associated with transcriptional regulatory elements with active epigenetic modifications. Promoter-proximal RNA polymerase II pausing promotes native G-quadruplex formation, oppositely, G-quadruplex stabilization by quadruplex-targeted ligands globally reduces RNA polymerase II occupancy at gene promoters as well as nascent RNA synthesis. Moreover, G-quadruplex stabilization modulates chromatin states and impedes transcription initiation via inhibiting the loading of general transcription factors to promoters.Together, these studies reveal a reciprocal regulation between native G-quadruplex dynamics and gene transcription in the genome, which will deepen our knowledge of G-quadruplex biology towards considering therapeutically targeting G-quadruplexes in human diseases.
2021-07-19 | GSE178668 | GEO
Project description:RNA secondary structures have been increasingly reported to serve critical regulatory roles in post-transcriptional gene regulation. RNA G-quadruplex secondary structures can serve as cis-elements to recruit splicing factors and regulate alternative RNA splicing. We recently showed that RNA G-quadruplexes play a critical regulatory role in regulating alternative splicing during the epithelial mesenchymal transition. Due to the critical role alternative splicing plays in human health and disease, an unmet need exists to identify small molecule modulators of alternative splicing. In this study, we performed high-throughput screening using a dual-output splicing reporter to identify small molecules capable of regulating alternative splicing by interacting with RNA secondary structure G-quadruplexes. We identify emetine and its analog cephaeline as small molecules that denature RNA G-quadruplexes in a sequence and location independent manner to modify alternative splicing. Transcriptome analysis reveals that treatment with emetine globally regulates alternative splicing, including events associated with exon-proximal G-quadruplexes. These data suggest a critical role for emetine and cephealine as splicing regulators with the selective ability to disrupt RNA G-quadruplex-associated alternative splicing in vivo.
2019-02-01 | GSE113505 | GEO
Project description:We report the RNA-seq data for rat nucleus pulposus cells after stabilizing G-Quadruplexes (G4). We sequenced rat nucleus pulposus cells treated with PDS, Braco-19 and Phen-DC3 separately and untreated with these G4 stabilizers, which could stabilize G4 structure in cells.
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Project description:We mapped CstF64-RNA interactions at the transcriptome level and studied CstF64-mediated regulation of global mRNA alternative polyadenylation by using iCLIP-seq and direct RNA sequencing analyses.
2012-10-01 | GSE40859 | GEO
Project description:Transcriptome-wide identification of transient RNA G-quadruplexes in human cells
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Project description:Enzymes of the TET family are methylcytosine dioxygenases that undergo frequent mutational or functional inactivation in both hematological and solid cancers. Recent studies have identified recurrent loss-of-function mutations in TET proteins in human patients with Diffuse Large B-Cell Lymphoma (DLBCL). Here we investigate the role of TET proteins in the pathogenesis of DLBCL by deleting the Tet2 and Tet3 genes in mature B cells in mice. Tet deletion perturbs mature B-cell homeostasis and causes spontaneous development of Germinal Center-derived B cell lymphomas. We show that an increase in G-quadruplexes and R-loops a common feature of TET deficiency in B cells as well as other hematopoietic cells. Genome-wide analyses revealed that G-quadruplexes and R-loops accumulated primarily near transcription start sites in TET-deficient B cells, and their accumulation correlated with increased DNA double-strand breaks. Moreover, CRISPR-mediated depletion of nucleases and helicases that regulate G-quadruplexes and R-loops led to decreased viability of TET-deficient but not control primary B cells. Our studies elucidate a molecular mechanism by which TET loss-of-function might predispose to development of B cell-derived and other malignancies, and highlight novel therapeutic avenues that could be further explored.
2021-10-28 | GSE161451 | GEO
Project description:We mapped CstF64-RNA interactions at the transcriptome level and studied CstF64-mediated regulation of global mRNA alternative polyadenylation by using iCLIP-seq and direct RNA sequencing analyses. CstF64 iCLIP-seq in HeLa cells; direct RNA sequencing (DRS) of control HeLa cells, CstF64-RNAi cells and CstF64&CstF64tau-RNAi cells
2012-10-01 | E-GEOD-40859 | biostudies-arrayexpress