Similar Datasets
Project description:HOTAIR lncRNA role in epithelial-mesenchymal transition
| PRJNA417082 | ENA
Project description:We characterize the TERRA transcriptome at normal and TRF2-depleted telomeres by RNA-seq and we demonstrate that TERRA upregulation is occurring at all transcribed telomeres upon depletion of TRF2. RNA-sequencing of HeLa mRNA, 4 samples: with or without TERRA enrichment by IP (respectively "IP" and "input"), with or without TFR-2 knock-down (respectively "_T" and "_EV").
2014-10-31 | E-GEOD-56727 | biostudies-arrayexpress
Project description:Through an integration of genomic and proteomic approaches to advance understanding of long noncoding RNAs, we investigate the function of the telomeric transcript, TERRA. By identifying thousands of TERRA target sites in the mouse genome, we demonstrate that TERRA can bind both in cis to telomeres and in trans to genic targets. We then define a large network of interacting proteins, including epigenetic factors, telomeric proteins, and the RNA helicase, ATRX. TERRA and ATRX share hundreds of target genes and are functionally antagonistic at these loci: whereas TERRA activates, ATRX represses gene expression. At telomeres, TERRA competes with telomeric DNA for ATRX binding, suppresses ATRX localization, and ensures telomeric stability. Depleting TERRA increases telomerase activity and induces telomeric pathologies, including formation of telomere-induced DNA damage foci and loss or duplication of telomeric sequences. We conclude that TERRA functions as an epigenomic modulator in trans and as an essential regulator of telomeres in cis.
2017-06-29 | GSE79180 | GEO
Project description:Telomerase-negative tumors can maintain telomere length by alternative lengthening of telomeres (ALT) but the mechanism of telomere maintenance in ALT cells is not well understood. A significant portion of the relapse Neuroblastoma (NB) tumors are positive for ALT which suggests better dissecting the ALT mechanism could provide novel therapeutic opportunities. TERRA RNA which is derived from the telomere ends is localized to telomeres in R-loop dependent manner and is essential for telomere maintenance. In the present study, we provide evidence that RNA modification at the N6 position of internal adenosine (m6A) in TERRA RNA by methyl transferase METTL3 is essential for telomere maintenance in ALT cells and loss of TERRA m6A/METTL3 leads to accumulation of DNA damage over telomere. Our data suggest that m6A modification in TERRA RNA is required for R-loop formation and telomere targeting of TERRA. We observed that R-loop enriched TERRA is abundantly m6A modified and m6A mediated recruitment of hnRNPA2B1 to TERRA RNA is essential for R-loop formation. Together our study suggests that m6A-mediated R-loop formation could be a widespread mechanism utilized by other chromatin-interacting lncRNAs. We also show treating ALT positive NB cells with small molecule METTL3 inhibitor leads to compromised telomere targeting of TERRA and accumulation of DNA damage over telomere, suggesting METTL3 inhibition could be a therapeutic opportunity for ALT positive NB.
2023-12-13 | GSE219212 | GEO
Project description:Telomerase-negative tumors can maintain telomere length by alternative lengthening of telomeres (ALT) but the mechanism of telomere maintenance in ALT cells is not well understood. A significant portion of the relapse Neuroblastoma (NB) tumors are positive for ALT which suggests better dissecting the ALT mechanism could provide novel therapeutic opportunities. TERRA RNA which is derived from the telomere ends is localized to telomeres in R-loop dependent manner and is essential for telomere maintenance. In the present study, we provide evidence that RNA modification at the N6 position of internal adenosine (m6A) in TERRA RNA by methyl transferase METTL3 is essential for telomere maintenance in ALT cells and loss of TERRA m6A/METTL3 leads to accumulation of DNA damage over telomere. Our data suggest that m6A modification in TERRA RNA is required for R-loop formation and telomere targeting of TERRA. We observed that R-loop enriched TERRA is abundantly m6A modified and m6A mediated recruitment of hnRNPA2B1 to TERRA RNA is essential for R-loop formation. Together our study suggests that m6A-mediated R-loop formation could be a widespread mechanism utilized by other chromatin-interacting lncRNAs. We also show treating ALT positive NB cells with small molecule METTL3 inhibitor leads to compromised telomere targeting of TERRA and accumulation of DNA damage over telomere, suggesting METTL3 inhibition could be a therapeutic opportunity for ALT positive NB.
2023-12-13 | GSE219146 | GEO