Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1110577 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:LIN28 is an RNA binding protein with important roles in early embryo development by interaction with let-7 microRNA precursors or mRNAs in cytoplasm. Here, we showed novel roles of LIN28 within the nucleolus in cultured pluripotent stem cells (PSCs). We found Lin28 deficiency led to activation of the 2-cell (2C)-like transcriptional program and repression of the ES cell program. Mechanistically, LIN28 maintains a peri-nucleolar heterochromatin-residing complex to repress 2C activator Dux via association with NCL and TRIM28. Meanwhile, it promotes liquid-liquid phase separation (LLPS) of nucleolar proteins FBL and NCL to support nucleolar function through its RNA binding domains and intrinsic disordered regions. These findings elucidate novel roles for nucleolar LIN28 in coordinately regulating the ES/2C state homeostasis, and shed light on RNA binding protein-mediated nucleolar phase separation mechanisms in PSCs and early embryo development.
2021-09-15 | GSE164221 | GEO
Project description:LIN28 is an RNA binding protein with important roles in early embryo development by interaction with let-7 microRNA precursors or mRNAs in cytoplasm. Here, we showed novel roles of LIN28 within the nucleolus in cultured pluripotent stem cells (PSCs). We found Lin28 deficiency led to activation of the 2-cell (2C)-like transcriptional program and repression of the ES cell program. Mechanistically, LIN28 maintains a peri-nucleolar heterochromatin-residing complex to repress 2C activator Dux via association with NCL and TRIM28. Meanwhile, it promotes liquid-liquid phase separation (LLPS) of nucleolar proteins FBL and NCL to support nucleolar function through its RNA binding domains and intrinsic disordered regions. These findings elucidate novel roles for nucleolar LIN28 in coordinately regulating the ES/2C state homeostasis, and shed light on RNA binding protein-mediated nucleolar phase separation mechanisms in PSCs and early embryo development.
2021-09-15 | GSE164130 | GEO
Project description:RNA-binding proteins emerge as effectors of the DNA damage response (DDR). The multifunctional non-POU domain-containing octamer-binding protein NONO/p54nrb marks nuclear paraspeckles in unperturbed cells, but also undergoes re-localisation to the nucleolus upon induction of DNA double-strand breaks (DSBs). However, NONO nucleolar re-localisation is poorly understood. Here we show that the topoisomerase-II inhibitor etoposide stimulates the production of RNA polymerase II-dependent, DNA damage-induced nucleolar antisense RNAs (diNARs) in human cancer cells. diNARs originate from distinct nucleolar intergenic spacer regions and form DNA-RNA hybrids to tether NONO to the nucleolus in ab RRM1 domain-dependent manner. NONO occupancy at protein-coding gene promoters is reduced by etoposide, which attenuates pre-mRNA synthesis, enhances NONO binding to pre-mRNA transcripts and is accompanied by nucleolar detention of a subset of such transcripts. The depletion or mutation of NONO interferes with detention and prolongs DSB signaling. Together, we describe a nucleolar DDR pathway that shields NONO and aberrant transcripts from DSBs to promote DNA repair.
2024-01-16 | GSE236899 | GEO
Project description:A considerable subset of gynecologic cancer patients’ experiences disease recurrence or acquired resistance, which contributes to high mortality rates in ovarian cancer (OC). Our prior studies showed that quinacrine (QC), an antimalarial drug, enhanced chemotherapy sensitivity in treatment-refractory OC cells, including artificially generated chemoresistant and high-grade serous OC cells. In this study, we investigated QC-induced transcriptomic changes to uncover its cytotoxic mechanisms of action. Isogenic pairs of OC cells generated to be chemo-resistant and chemo-sensitive counterparts were treated with QC followed by RNAseq analysis. Validation of selected expression results and database comparison analyses indicated the ribosomal biogenesis (RBG) pathway is inhibited by QC. RBG is commonly upregulated in cancer cells and is emerging as a drug target. We found that QC attenuates the in vitro and in in vivo expression of nucleostemin (NS/GNL3), a nucleolar RBG and DNA repair protein, and the RPA194 catalytic subunit of Pol I that results in RBG inhibition and nucleolar stress. QC promotes the redistribution of fibrillarin in form of extranuclear foci and nucleolar caps, an indicator of nucleolar stress conditions. In addition, we found that QC-induced downregulation of NS disrupted homologous recombination repair both by reducing NS protein levels and parylation resulting in reduced RAD51 recruitment to DNA damage. Our data suggests that QC inhibits RBG and this inhibition promotes DNA damage by directly downregulating the NS-RAD51 interaction. Additionally, QC showed strong synergy with PARP inhibitors in OC cells. Overall, we found that QC by downregulates the RBG pathway, induces nucleolar stress, supports the increase of DNA damage, and sensitized cells to PARP inhibition, which supports new therapeutic stratagems for treatment-refractory OC. Our work offers support for targeting RBG in OC and determines NS to be a novel target for QC.
2021-09-29 | GSE176246 | GEO
Project description:LIN28 is an RNA binding protein with important roles in early embryo development by interaction with let-7 microRNA precursors or mRNAs in cytoplasm. Here, we showed novel roles of LIN28 within the nucleolus in cultured pluripotent stem cells (PSCs). We found Lin28 deficiency led to activation of the 2-cell (2C)-like transcriptional program and repression of the ES cell program. Mechanistically, LIN28 maintains a peri-nucleolar heterochromatin-residing complex to repress 2C activator Dux via association with NCL and TRIM28. Meanwhile, it promotes liquid-liquid phase separation (LLPS) of nucleolar proteins FBL and NCL to support nucleolar function through its RNA binding domains and intrinsic disordered regions. These findings elucidate novel roles for nucleolar LIN28 in coordinately regulating the ES/2C state homeostasis, and shed light on RNA binding protein-mediated nucleolar phase separation mechanisms in PSCs and early embryo development.
2021-09-15 | GSE164238 | GEO
Project description:LIN28 is an RNA binding protein with important roles in early embryo development by interaction with let-7 microRNA precursors or mRNAs in cytoplasm. Here, we showed novel roles of LIN28 within the nucleolus in cultured pluripotent stem cells (PSCs). We found Lin28 deficiency led to activation of the 2-cell (2C)-like transcriptional program and repression of the ES cell program. Mechanistically, LIN28 maintains a peri-nucleolar heterochromatin-residing complex to repress 2C activator Dux via association with NCL and TRIM28. Meanwhile, it promotes liquid-liquid phase separation (LLPS) of nucleolar proteins FBL and NCL to support nucleolar function through its RNA binding domains and intrinsic disordered regions. These findings elucidate novel roles for nucleolar LIN28 in coordinately regulating the ES/2C state homeostasis, and shed light on RNA binding protein-mediated nucleolar phase separation mechanisms in PSCs and early embryo development.
2021-09-15 | GSE164414 | GEO
Project description:LIN28 is an RNA binding protein with important roles in early embryo development by interaction with let-7 microRNA precursors or mRNAs in cytoplasm. Here, we showed novel roles of LIN28 within the nucleolus in cultured pluripotent stem cells (PSCs). We found Lin28 deficiency led to activation of the 2-cell (2C)-like transcriptional program and repression of the ES cell program. Mechanistically, LIN28 maintains a peri-nucleolar heterochromatin-residing complex to repress 2C activator Dux via association with NCL and TRIM28. Meanwhile, it promotes liquid-liquid phase separation (LLPS) of nucleolar proteins FBL and NCL to support nucleolar function through its RNA binding domains and intrinsic disordered regions. These findings elucidate novel roles for nucleolar LIN28 in coordinately regulating the ES/2C state homeostasis, and shed light on RNA binding protein-mediated nucleolar phase separation mechanisms in PSCs and early embryo development.
2021-09-15 | GSE164418 | GEO
Project description:LIN28 is an RNA binding protein with important roles in early embryo development by interaction with let-7 microRNA precursors or mRNAs in cytoplasm. Here, we showed novel roles of LIN28 within the nucleolus in cultured pluripotent stem cells (PSCs). We found Lin28 deficiency led to activation of the 2-cell (2C)-like transcriptional program and repression of the ES cell program. Mechanistically, LIN28 maintains a peri-nucleolar heterochromatin-residing complex to repress 2C activator Dux via association with NCL and TRIM28. Meanwhile, it promotes liquid-liquid phase separation (LLPS) of nucleolar proteins FBL and NCL to support nucleolar function through its RNA binding domains and intrinsic disordered regions. These findings elucidate novel roles for nucleolar LIN28 in coordinately regulating the ES/2C state homeostasis, and shed light on RNA binding protein-mediated nucleolar phase separation mechanisms in PSCs and early embryo development.
2021-09-15 | GSE164296 | GEO
Project description:DEAD-box RNA helicase 21 (DDX21), is a nucleolar protein harboring ATP-dependent double-stranded RNA unwinding activities, essential in rRNA processing and ribosome biogenesis. However, its role in colorectal cancer (CRC) progression remains unclear. In this study, we performed RNAseq in colorectal cancer line HCT8 with or without DDX21 gene silencing, to reveal the role of DDX21 in transcriptional and epigenetic control of CRC cell proliferation.
2022-04-07 | GSE184726 | GEO
Project description:RNA-binding proteins emerge as effectors of the DNA damage response (DDR). The multifunctional non-POU domain-containing octamer-binding protein NONO/p54nrb marks nuclear paraspeckles in unperturbed cells, but also undergoes re-localisation to the nucleolus upon induction of DNA double-strand breaks (DSBs). However, NONO nucleolar re-localisation is poorly understood. Here we show that the topoisomerase-II inhibitor etoposide stimulates the production of RNA polymerase II-dependent, DNA damage-induced nucleolar antisense RNAs (diNARs) in human cancer cells. diNARs originate from distinct nucleolar intergenic spacer regions and form DNA-RNA hybrids to tether NONO to the nucleolus in ab RRM1 domain-dependent manner. NONO occupancy at protein-coding gene promoters is reduced by etoposide, which attenuates pre-mRNA synthesis, enhances NONO binding to pre-mRNA transcripts and is accompanied by nucleolar detention of a subset of such transcripts. The depletion or mutation of NONO interferes with detention and prolongs DSB signaling. Together, we describe a nucleolar DDR pathway that shields NONO and aberrant transcripts from DSBs to promote DNA repair.
2024-01-16 | GSE236888 | GEO