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DHX36-mediated G-quadruplexes unwinding is essential for oocyte and early embryo development in mice

ABSTRACT: DHX36-mediated G-quadruplexes unwinding is essential for oocyte and early embryo development in mice

PROVIDER: PRJNA1108676 | ENA |

REPOSITORIES: ENA

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DHX36-mediated G-quadruplexes unwinding is essential for oocyte and early embryo development in mice

Project description:The role of G-quadruplex (G4) structures and their effects on oocyte and early embryo development remain unclear. We discovered that the G4 helicase DHX36 is essential for oocyte growth and the maternal-to-zygotic transition (MZT). Conditional knockout of DHX36 resulted in DNA G4 accumulation in mouse oocytes, reducing chromatin accessibility, and inhibiting RNA transcription, ultimately disrupting transcriptome homeostasis during oocyte growth and MZT.

2025-01-29 | GSE266915 | GEO

DHX36-mediated G-quadruplexes unwinding is essential for oocyte and early embryo development in mice

Project description:The role of G-quadruplex (G4) structures and their effects on meiosis resumption and early embryo development remain unclear. We discovered that the G4 helicase DHX36 is essential for oocyte growth and the maternal-to-zygotic transition (MZT). Conditional knockout of DHX36 resulted in DNA G4 accumulation in mouse oocytes, reducing chromatin accessibility, and inhibiting RNA transcription, ultimately disrupting transcriptome homeostasis during oocyte growth and MZT.

2025-01-29 | GSE266885 | GEO

DHX36-mediated G-quadruplexes unwinding is essential for oocyte and early embryo development in mice

Project description:DHX36-mediated G-quadruplexes unwinding is essential for oocyte and early embryo development in mice

| PRJNA1108710 | ENA

System-wide analysis of Dhx36 function in skeletal muscle satellite cells reveals its binding with 5’UTR G4 structure to promote Gnai2 RNA translation [Polysome profiling]

Project description:In this study, we deciphered the functions of Dhx36 and related molecular mechanisms in muscle stem cells and muscle regeneration. We found Dhx36 was highly induced in activated muscle stem cells during regeneration induced by injury. Conditional inactivation of Dhx36 in mouse muscle stem cells caused significant impaired regeneration, which was due to the dramatically decreased cell proliferation. Dhx36 was a well-known RNA helicase for binding/unwinding DNA/RNA G-quadruplexes and it was dominantly expressed in cytoplasm of proliferating myoblast. To examine whether Dhx36 regulates translation process, we conducted polysome profiling followed by RNA-seq in WT and Dhx36 KO myoblast cells.

2021-04-27 | GSE151123 | GEO

System-wide analysis of Dhx36 function in skeletal muscle satellite cells reveals its binding with 5’UTR G4 structure to promote Gnai2 RNA translation

Project description:In this study, we deciphered the functions of Dhx36 and related molecular mechanisms in muscle stem cells and muscle regeneration. We found Dhx36 was highly induced in activated muscle stem cells during regeneration induced by injury. Conditional inactivation of Dhx36 in mouse muscle stem cells caused significant impaired regeneration, which was due to the dramatically decreased cell proliferation. Dhx36 was a well-known RNA helicase for binding/unwinding DNA/RNA G-quadruplexes and it was dominantly expressed in cytoplasm of proliferating myoblast. CLIP-seq was conducted to identify the mRNAs interacting with Dhx36 in myoblast cells. To examine whether Dhx36 regulates translation process, we also conducted polysome profiling followed by RNA-seq in WT and Dhx36 KO myoblast cells. This SuperSeries is composed of the SubSeries listed below.

2021-04-27 | GSE151124 | GEO

SMaRT lncRNA controls translation of a G-quadruplex containing mRNA antagonizing the DHX36 helicase

Project description:Guanine-quadruplexes (G4) present in RNA and DNA exert a number of different functions in the nucleus and in the cytoplasm. However, the molecular mechanisms of G4-mediated regulation are still poorly understood. We describe a regulatory circuitry operating in the early phases of muscle differentiation in which a long non coding RNA (SMaRT) base pairs with a G4-containing mRNA (Mlx-g) and represses its translation in an antagonistic way with the RNA helicase DHX36. MLX-g is required to allow the nuclear translocation of the MLX-a and b dimerization partners and to control proper myogenesis. We show that by controlling MLX-g, lnc-SMaRT is able to regulate the overall quantity of nuclear MLX proteins and their transcriptional output. Therefore, the circuitry composed by lnc-SMaRT, Mlx-g and Dhx36 not only plays an important role in the control of myogenesis but unravels a molecular mechanism where G4 structures and G4 unwinding activities are controlled in vivo.

2020-03-18 | GSE128486 | GEO

System-wide analysis of Dhx36 function in skeletal muscle satellite cells reveals its binding with 5’UTR G4 structure to promote Gnai2 RNA translation [CLIP-seq]

Project description:In this study, we deciphered the functions of Dhx36 and related molecular mechanisms in muscle stem cells and muscle regeneration. We found Dhx36 was highly induced in activated muscle stem cells during regeneration induced by injury. Conditional inactivation of Dhx36 in mouse muscle stem cells caused significant impaired regeneration, which was due to the dramatically decreased cell proliferation. Dhx36 was a well-known RNA helicase for binding/unbinding DNA/RNA G-quadruplexes and it was dominantly expressed in cytoplasm of proliferating myoblast. Therefore CLIP-seq was conducted to identify the mRNAs interacting with Dhx36 in myoblast cells.

2021-04-27 | GSE151122 | GEO

The translational oscillation in oocyte and early embryo development

Project description:Translation is critical for development as transcription in the oocyte and early embryo is silenced. To illustrate the translational changes during meiosis and consecutive two mitoses of the oocyte and early embryo, we performed a genome-wide translatome analysis. Acquired data showed significant and uniform activation of key translational initiation and elongation axes specific to M-phases. Although global protein synthesis decreases in M-phases, translation initiation and elongation activity increases in a uniformly fluctuating manner, leading to qualitative changes in translation regulation via the mTOR1/4F/eEF2 axis. Overall, we have uncovered a highly dynamic and oscillatory pattern of translational reprogramming that contributes to the translational regulation of specific mRNAs with different modes of polysomal occupancy/translation that are important for oocyte and embryo developmental competence. Our results provide new insights into the regulation of gene expression during oocyte meiosis as well as the first two embryonic mitoses and show, how temporal translation can be optimized. This study is the first step towards a comprehensive analysis of the molecular mechanisms that not only control translation during early development, but also regulate translation-related networks employed in the oocyte-to-embryo transition and embryonic genome activation.

2023-05-29 | GSE230016 | GEO

BLM helicase protein negatively regulates stress granule formation through unwinding RNA G-quadruplex structures

Project description:Bloom’s syndrome (BLM) protein is a known nuclear helicase that is able to unwind DNA secondary structures such as G-quadruplexes. However, its role in the regulation of cytoplasmic processes that involve RNA G-quadruplexes (rG4s) has not been previously studied. Here, we demonstrate that BLM is recruited to stress granules (SGs), which are cytoplasmic biomolecular condensates composed of RNA-binding proteins and RNAs. BLM is enriched in SGs upon different stress conditions and in an rG4-dependent manner. We show that BLM unwinds rG4s efficiently, thus acting as a negative regulator of SG formation, potentially via its unwinding function. Altogether, our data expand the cellular activity of BLM and shed light on the function that helicases play in the dynamics of biomolecular condensates.

2023-10-24 | PXD039534 | Pride

Zebrafish Ski7 tunes RNA levels during the oocyte-to-embryo transition

Project description:Post-transcriptional mechanisms are crucial for the regulation of gene expression. These mechanisms are particularly important during rapid developmental transitions such as the oocyte-to-embryo transition, which is characterized by dramatic changes to the developmental program in the absence of nuclear transcription. Under these conditions, changes to the RNA content are solely dependent on RNA degradation. Although several mechanisms that promote RNA decay during embryogenesis have been identified, it remains unclear which cellular machineries contribute to remodeling the maternal transcriptome during the oocyte-to-embryo transition. Here, we focused on the auxiliary 3’-to-5’ degradation factor Ski7 in zebrafish as its mRNA peaks during this time frame. Homozygous ski7 mutant fish were viable and developed into morphologically normal adults, yet they had decreased fertility. Consistent with the idea that Ski7 participates in remodeling the transcriptome during the oocyte-to-embryo transition, transcriptome profiling identified stage-specific mRNA targets of Ski7. Genes upregulated in ski7 mutants were generally lowly expressed in wild type, suggesting that Ski7 maintains low transcript levels for this subset of genes. GO enrichment analyses of genes mis-regulated in ski7 mutants implicated Ski7 in the regulation of redox processes. This was confirmed experimentally by an increased resistance of ski7 mutant embryos to reductive stress. Overall, our results provide first insights into the physiological role of vertebrate Ski7 as an important post-transcriptional regulator during the oocyte-to-embryo transition.

2021-02-12 | GSE147112 | GEO

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