Similar Datasets
Project description:During vertebrate embryogenesis, hematopoietic stem and progenitor cell (HSPC) production through endothelial-to-hematopoietic transition requires suitable developmental signals, but how these signals are accurately regulated remains incompletely understood. Cytoplasmic polyadenylation, which is one of the posttranscriptional regulations, plays a crucial role in RNA metabolism. Here, we report that Cpeb1b-mediated cytoplasmic polyadenylation is important for HSPC specification by translational control of Hedgehog (Hh) signaling during zebrafish early development. Cpeb1b is highly expressed in notochord and its deficiency results in defective HSPC production. Mechanistically, Cpeb1b regulates hemogenic endothelium specification by the Hedgehog–Vegf–Notch axis. We demonstrate that the cytoplasmic polyadenylation element motif-dependent interaction between Cpeb1b and shha messenger RNA (mRNA) in the liquid-like condensates, which are induced by Pabpc1b phase separation, is required for cytoplasmic polyadenylation of shha mRNA. Intriguingly, the cytoplasmic polyadenylation regulates translation but not stability of shha mRNA, which further enhances the Shha protein level and Hh signal transduction. Taken together, our findings uncover the role of Cpeb1b-mediated cytoplasmic polyadenylation in HSPC development and provide insights into how posttranscriptional regulation can direct developmental signals with high fidelity to translate them into cell fate transition.
2023-02-06 | GSE207906 | GEO
Project description:The translational reactivation of maternal mRNAs encoding the drivers of vertebrate meiosis is accomplished mainly by cytoplasmic polyadenylation. The Cytoplasmic Polyadenylation Elements (CPEs) present in the 3’ UTR of these transcripts, together with their cognate CPE-binding proteins (CPEBs), define a combinatorial code that determines the timing and extent of translational activation upon meiosis resumption. In addition, the RNA-binding protein Musashi1 (Msi1) regulates the polyadenylation of CPE-containing mRNAs by an as yet undefined CPEB-dependent or -independent mechanism. Here we show that Msi1 alone does not support cytoplasmic polyadenylation, but its binding triggers the remodeling of RNA structure, thereby exposing adjacent CPEs and stimulating polyadenylation. Thus, Msi1 directs the preferential use of specific CPEs, which in turn affects the timing and extent of polyadenylation during meiotic progression. Genome-wide analysis of CPEB1- and Msi-associated mRNAs identified 491 common targets, thus revealing a new layer of CPE-mediated translational control.
2017-07-17 | GSE68098 | GEO
Project description:The translational reactivation of maternal mRNAs encoding the drivers of vertebrate meiosis is accomplished mainly by cytoplasmic polyadenylation. The Cytoplasmic Polyadenylation Elements (CPEs) present in the 3’ UTR of these transcripts, together with their cognate CPE-binding proteins (CPEBs), define a combinatorial code that determines the timing and extent of translational activation upon meiosis resumption. In addition, the RNA-binding protein Musashi1 (Msi1) regulates the polyadenylation of CPE-containing mRNAs by an as yet undefined CPEB-dependent or -independent mechanism. Here we show that Msi1 alone does not support cytoplasmic polyadenylation, but its binding triggers the remodeling of RNA structure, thereby exposing adjacent CPEs and stimulating polyadenylation. Thus, Msi1 directs the preferential use of specific CPEs, which in turn affects the timing and extent of polyadenylation during meiotic progression. Genome-wide analysis of CPEB1- and Msi-associated mRNAs identified 491 common targets, thus revealing a new layer of CPE-mediated translational control.
2017-07-17 | GSE68097 | GEO
Project description:The translational reactivation of maternal mRNAs encoding the drivers of vertebrate meiosis is accomplished mainly by cytoplasmic polyadenylation. The Cytoplasmic Polyadenylation Elements (CPEs) present in the 3’ UTR of these transcripts, together with their cognate CPE-binding proteins (CPEBs), define a combinatorial code that determines the timing and extent of translational activation upon meiosis resumption. In addition, the RNA-binding protein Musashi1 (Msi1) regulates the polyadenylation of CPE-containing mRNAs by an as yet undefined CPEB-dependent or -independent mechanism. Here we show that Msi1 alone does not support cytoplasmic polyadenylation, but its binding triggers the remodeling of RNA structure, thereby exposing adjacent CPEs and stimulating polyadenylation. Thus, Msi1 directs the preferential use of specific CPEs, which in turn affects the timing and extent of polyadenylation during meiotic progression. Genome-wide analysis of CPEB1- and Msi-associated mRNAs identified 491 common targets, thus revealing a new layer of CPE-mediated translational control.
2017-07-17 | GSE68095 | 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:Cytoplasmic polyadenylation is a mechanism to promote mRNA translation in a wide variety of biological contexts.The conserved RNA-binding protein family CPEB has been shown to mediate canonical cytoplasmic polyadenylation of target transcripts. We have previously reported evidence for RNA-interference factor Dicer-2 as a component of a non-canonical complex, that operates independent of CPEB in Drosophila. In this study, we investigate Dicer-2 mRNA targets and protein co-factors in cytoplasmic polyadenylation. Using RIP‐Seq analysis we identify hundreds of potential Dicer-2 target transcripts, ~60% of which were previously found as targets of the cytoplasmic poly(A) polymerase Wispy, suggesting widespread roles of Dicer-2 in cytoplasmic polyadenylation. Large-scale immunoprecipitation and mass spectrometry revealed Ataxin-2 and Twenty-four among the high-confidence interactors of Dicer-2. Complex analyses indicated that both factors form an RNA‐independent complex with Dicer‐2, and mediate interactions of Dicer‐2 with Wispy. Functional poly(A)‐test analyses showed that Twenty‐four and Ataxin-2 are required for cytoplasmic polyadenylation of a subset of Dicer‐2 targets. Our results reveal components of a novel cytoplasmic polyadenylation complex that operates during Drosophila early embryogenesis.
2022-08-30 | PXD030281 | Pride
Project description:The Cytoplasmic Polyadenylation Element Binding (CPEB)-family of RNA-binding proteins regulates pre-mRNA processing and translation of CPE-containing mRNAs in early embryonic development and synaptic activity. However, the specific functions of each CPEB in the adult organism are poorly understood. Here we show that CPEB4 is required to suppress high fat diet- and aging-induced endoplasmic reticulum (ER) stress, and its subsequent hepatic steatosis. Stress-activated expression of CPEB4 in the liver is controlled through a double layer of regulation. First, Cpeb4 is transcriptionally regulated by the circadian clock and then, its mRNA translation is regulated by the Unfolded Protein Response (UPR) through the upstream Open Reading Frames (uORFs) present in its 5’ UTR. Thus, CPEB4 is synthesized only upon ER-stress but the amplitude of the induction is circadian. In turn, CPEB4 activates a second wave of UPR-translation required to maintain ER and mitochondrial homeostasis. Our results suggest that combined transcriptional and translational regulation of CPEB4 generates a “circadian mediator”, which
coordinates the hepatic UPR activity with periods of high ER protein-folding demand preventing non-alcoholic fatty liver disease (NAFLD).
2017-01-16 | GSE81876 | 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:During oocyte maturation and early embryonic development, poly(A)-tail lengths strongly influence mRNA translation. However, how tail lengths are controlled at different developmental stages has been unclear. Here, we performed tail-length and translational profiling of mRNA reporter libraries (each with > 10 million 3ʹ-UTR sequence variants) in frog oocytes and embryos, and fish embryos. These analyses revealed that the UUUUA motif specifies cytoplasmic polyadenylation and identified diverse context features that modulate the activity of this 5-mer. Additional sequence motifs drive stage-specific deadenylation in embryos, and UUUUA and C-rich motifs drive tail-length-independent translational repression in oocytes. A neural network model accurately predicts tail-length change during oocyte maturation in frogs, mice, and humans. Analyses of human sequence variants showed that those predicted to disrupt tail-length control have been under negative selection, implying that our insights into control of poly(A)-tail length and translation have implications for human health and fertility.
2024-02-15 | GSE241107 | GEO
Project description:Ageing-associated proteome and acetylome of hematopoietic progenitor cells
2020-09-24 | PXD021651 | iProX