Phase separation of Ddx3xb helicase regulates maternal-to-zygotic transition in zebrafish
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ABSTRACT:
PROVIDER: PRJNA715459 | ENA |
REPOSITORIES: ENA
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Project description:We show that liquid-liquid phase separation (LLPS)-mediated zebrafish Ddx3xb condensation facilitates MZT through promoting maternal mRNAs translation. Ddx3xb forms condensates via its N-terminal intrinsically disordered regions (IDRs), and the gradually increased ATP concentration after fertilization promotes its aggregation capability. Ddx3xb-deficiency decelerates the decay of maternal mRNAs and impedes zygotic genome activation, further leading to developmental defect. The phenotype in Ddx3xb-deficiency embryos can be efficiently rescued by condensed Ddx3xb, but not the Ddx3xb without LLPS ability. Mechanistically, the condensation of Ddx3xb is vital for its RNA helicase activity, which is critical for involved in promoting translation efficiency of maternal mRNAs through opening 5’ UTR structures during the MZT process. Our study demonstrates that the condensation of Ddx3xb promotes maternal mRNAs translation via its RNA unwinding activity and further facilitates MZT, highlighting the critical role of protein phase separation in translational control and animal early development.
2022-06-03 | GSE181503 | GEO
Project description:We show that liquid-liquid phase separation (LLPS)-mediated zebrafish Ddx3xb condensation facilitates MZT through promoting maternal mRNAs translation. Ddx3xb forms condensates via its N-terminal intrinsically disordered regions (IDRs), and the gradually increased ATP concentration after fertilization promotes its aggregation capability. Ddx3xb-deficiency decelerates the decay of maternal mRNAs and impedes zygotic genome activation, further leading to developmental defect. The phenotype in Ddx3xb-deficiency embryos can be efficiently rescued by condensed Ddx3xb, but not the Ddx3xb without LLPS ability. Mechanistically, the condensation of Ddx3xb is vital for its RNA helicase activity, which is critical for involved in promoting translation efficiency of maternal mRNAs through opening 5’ UTR structures during the MZT process. Our study demonstrates that the condensation of Ddx3xb promotes maternal mRNAs translation via its RNA unwinding activity and further facilitates MZT, highlighting the critical role of protein phase separation in translational control and animal early development.
2022-06-03 | GSE169161 | GEO
Project description:We show that liquid-liquid phase separation (LLPS)-mediated zebrafish Ddx3xb condensation facilitates MZT through promoting maternal mRNAs translation. Ddx3xb forms condensates via its N-terminal intrinsically disordered regions (IDRs), and the gradually increased ATP concentration after fertilization promotes its aggregation capability. Ddx3xb-deficiency decelerates the decay of maternal mRNAs and impedes zygotic genome activation, further leading to developmental defect. The phenotype in Ddx3xb-deficiency embryos can be efficiently rescued by condensed Ddx3xb, but not the Ddx3xb without LLPS ability. Mechanistically, the condensation of Ddx3xb is vital for its RNA helicase activity, which is critical for involved in promoting translation efficiency of maternal mRNAs through opening 5’ UTR structures during the MZT process. Our study demonstrates that the condensation of Ddx3xb promotes maternal mRNAs translation via its RNA unwinding activity and further facilitates MZT, highlighting the critical role of protein phase separation in translational control and animal early development.
2022-06-03 | GSE169166 | GEO
Project description:We show that liquid-liquid phase separation (LLPS)-mediated zebrafish Ddx3xb condensation facilitates MZT through promoting maternal mRNAs translation. Ddx3xb forms condensates via its N-terminal intrinsically disordered regions (IDRs), and the gradually increased ATP concentration after fertilization promotes its aggregation capability. Ddx3xb-deficiency decelerates the decay of maternal mRNAs and impedes zygotic genome activation, further leading to developmental defect. The phenotype in Ddx3xb-deficiency embryos can be efficiently rescued by condensed Ddx3xb, but not the Ddx3xb without LLPS ability. Mechanistically, the condensation of Ddx3xb is vital for its RNA helicase activity, which is critical for involved in promoting translation efficiency of maternal mRNAs through opening 5’ UTR structures during the MZT process. Our study demonstrates that the condensation of Ddx3xb promotes maternal mRNAs translation via its RNA unwinding activity and further facilitates MZT, highlighting the critical role of protein phase separation in translational control and animal early development.
2022-06-03 | GSE169163 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2022-06-03 | GSE169169 | GEO
Project description:We show that liquid-liquid phase separation (LLPS)-mediated zebrafish Ddx3xb condensation facilitates MZT through promoting maternal mRNAs translation. Ddx3xb forms condensates via its N-terminal intrinsically disordered regions (IDRs), and the gradually increased ATP concentration after fertilization promotes its aggregation capability. Ddx3xb-deficiency decelerates the decay of maternal mRNAs and impedes zygotic genome activation, further leading to developmental defect. The phenotype in Ddx3xb-deficiency embryos can be efficiently rescued by condensed Ddx3xb, but not the Ddx3xb without LLPS ability. Mechanistically, the condensation of Ddx3xb is vital for its RNA helicase activity, which is critical for involved in promoting translation efficiency of maternal mRNAs through opening 5’ UTR structures during the MZT process. Our study demonstrates that the condensation of Ddx3xb promotes maternal mRNAs translation via its RNA unwinding activity and further facilitates MZT, highlighting the critical role of protein phase separation in translational control and animal early development.
2022-06-03 | GSE169168 | GEO
Project description:Maternal-to-zygotic transition (MZT) is a conserved and fundamental process during which the maternal environment of oocyte transits to the zygotic genome driven expression program, and terminally differentiated oocyte and sperm are reprogrammed to totipotency. It is initiated by maternal mRNAs and proteins during the period of zygotic genome quiescence after fertilization, followed by a gradual switch to zygotic genome activation and accompanied by clearance of maternal RNAs and proteins. A key question for embryonic development is how MZT process is regulated. Here we used a low-input proteomic analysis to measure the proteomic dynamics during early development of mouse maternal-to-zygotic transition.
2023-03-27 | PXD041023 | Pride
Project description:Upon fertilization, maternal factors direct development in a transcriptionally silent embryo. At the maternal-to-zygotic transition (MZT), a universal step in animal development, unknown maternal factors trigger zygotic genome activation (ZGA). In zebrafish, ZGA is required for gastrulation and clearance of maternal mRNAs, which is achieved in part by the conserved microRNA miR-430. However, the precise factors that activate the zygotic program remain largely unknown. Here we show that Nanog, Pou5f1 and SoxB1 are required for genome activation in zebrafish. We identified several hundred genes directly activated by maternal factors, thus constituting the first wave of zygotic transcription in zebrafish. Ribosome profiling in the pre-MZT embryo revealed that nanog, sox19b and pou5f1 are the most highly translated transcription factor mRNAs. Combined loss of function for Nanog, SoxB1 and Pou5f1 resulted in developmental arrest prior to gastrulation, and a failure to activate >75% of zygotic genes. Furthermore, we found that Nanog binds the miR-430 locus and together with Pou5f1 and SoxB1 initiate miR-430 expression and activity. Our results demonstrate that maternal Nanog, Pou5f1 and SoxB1 are required to initiate the zygotic developmental program and in turn trigger the clearance of the maternal program by activating miR-430 expression. Wild type and loss-of-function total mRNA sequencing of embryonic transcriptomes pre- and post-MZT; ribosome profiling pre-MZT
2013-09-22 | E-GEOD-47558 | biostudies-arrayexpress
Project description:Chromosome translocation is known to generate oncogenes such as SS18-SSX1, but the underlying mechanism remains unknown. Here we show that enhanced phase separation acquired by translocation mediates oncogenic transformation. SSX fusion dramatically enhances the phase separation property of SS18 protein through H2AK119ub. Super condensates generated by SS18-SSX recruit acetyltransferases CBP/P300 as wild type SS18, but exclude HDACs such that H3K27ac accumulates abnormally at loci from those normally occupied by SS18, resulting aberrant silencing and activation of target genes. Consistently, we show that inhibition of H3K27ac can attenuate the tumorigenicity of the fusion oncoprotein. These results provide the first case for phase separation as a transforming event to generate oncogene and super phase separation can be targeted for cancer therapy.
2024-05-24 | GSE240467 | GEO
Project description:Chromosome translocation is known to generate oncogenes such as SS18-SSX1, but the underlying mechanism remains unknown. Here we show that enhanced phase separation acquired by translocation mediates oncogenic transformation. SSX fusion dramatically enhances the phase separation property of SS18 protein through H2AK119ub. Super condensates generated by SS18-SSX recruit acetyltransferases CBP/P300 as wild type SS18, but exclude HDACs such that H3K27ac accumulates abnormally at loci from those normally occupied by SS18, resulting aberrant silencing and activation of target genes. Consistently, we show that inhibition of H3K27ac can attenuate the tumorigenicity of the fusion oncoprotein (we do not have the data in your figures?). These results provide the first case for phase separation as a transforming event to generate oncogene and super phase separation can be targeted for cancer therapy.
2024-05-24 | GSE211455 | GEO