Biology subjects

Dvoran, M.

Publications and source records attributed to Dvoran, M..

3 recordsLinked to original sources

bioRxiv2024

Absence of CDK12 in oocyte leads to female infertility

Transcriptional activity and gene expression are essential for the development of a mature, meiotically competent oocyte. We have found that the absence of cyclin-dependent kinase 12 (CDK12) in oocytes leads to complete female sterility, as there are no fully developed oocytes able to accomplish meiosis I in the ovaries. Mechanistically, CDK12 in growing oocytes controls POLII activity and maintenance of the physiological maternal transcriptome, which negatively affects protein synthesis that promotes further oocyte growth. In addition, disruption of oocyte development disrupts folliculogenesis, resulting in a premature failure phenotype without terminal folliculogenesis and ovulation. In summary, we have characterized a single master regulator of the oocyte transcriptional program and gene expression that is essential for oocyte growth and female fertility. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=113 HEIGHT=200 SRC="FIGDIR/small/622910v1_ufig1.gif" ALT="Figure 1"> View larger version (16K): org.highwire.dtl.DTLVardef@179b286org.highwire.dtl.DTLVardef@b7a847org.highwire.dtl.DTLVardef@1890a35org.highwire.dtl.DTLVardef@1fd2798_HPS_FORMAT_FIGEXP M_FIG C_FIG

developmental biology↗

bioRxiv2024

Spatiotemporal dynamics and selectivity of mRNA translation during mouse pre-implantation development

Translational regulation is pivotal during preimplantation development. However, how mRNAs are selected for temporal regulation and their dynamic utilization and fate during this period are still unknown. Using a high-resolution ribosome profiling approach, we analyzed the transcriptome, as well as monosome- and polysome-bound RNAs of mouse oocytes and embryos, defining an unprecedented extent of spatiotemporal translational landscapes during this rapid developmental phase. We observed previously unknown mechanisms of translational selectivity, i.e., stage-wise deferral of loading monosome-bound mRNAs to polysome for active translation, continuous translation of both monosome and polysome-bound mRNAs at the same developmental stage, and priming to monosomes after initial activation. We showed that a eukaryotic initiation factor Eif1ad3, which is exclusively translated in the 2-Cell embryo, is required for ribosome biogenesis post embryonic genome activation. Our study thus provides genome-wide datasets and analyses of spatiotemporal translational dynamics accompanying mammalian germ cell and embryonic development and reveals the contribution of a novel translation initiation factor to mammalian pre-implantation development.

developmental biology↗

bioRxiv2022

High-resolution Ribosome Profiling Reveals Translational Selectivity for Transcripts in Bovine Preimplantation Embryo Development

High resolution ribosome fractionation and low-input ribosome profiling of bovine oocytes and preimplantation embryos has enabled us to define the translational landscapes of early embryo development at an unprecedented level. We analyzed the transcriptome, polysome- and non-polysome-bound RNA profiles of bovine oocytes (GV and MII stage) and early embryos at 2-, 8-cell, morula, and blastocyst stage, and revealed four modes of translational selectivity: i. selective translation of non-abundant mRNAs, ii. active, but modest translation of a selection of highly expressed mRNAs, iii. translationally suppressed abundant to moderately abundant mRNAs, and iv. mRNAs associated specifically with monosomes. A strong translational selection of low abundance mRNAs encoding protein components involved in metabolic pathways and lysosome was found throughout bovine oocyte and preimplantation development. In particular, genes encoding components involved in mitochondrial function were prioritized for translation. Notably, transcripts encoding proteins regulating chromatin modifications selectively translated in oocytes. We found that the translational dynamics largely reflects transcriptional profiles in oocytes and 2-cell embryos, but observed marked shift in translational control in 8-cell embryos associated with the main phase of embryonic genome activation. Subsequently, transcription and translation become better synchronized in morulae and blastocysts. Together, these data reveal a unique spatiotemporal translational regulation that accompanies bovine preimplantation development. Significance StatementTranslational control during preimplantation embryo development is poorly understood, mostly due to the scarcity of samples and the corresponding inability to analyze low quantities of these materials. By developing a low-input method, we have been able to explore the transcriptome, polysome- and non-polysome-bound RNA profiles of bovine oocytes (GV and MII stage) and preimplantation embryos at 2-, 8-cell, morula, and blastocyst stages. We reveal four different modes of translational selectivity, plus novel temporal regulatory mechanisms during early embryo development. The spatiotemporal translation dynamics of bovine oocytes and preimplantation embryos offer an entirely new insight into mammalian embryo development research and new possibilities for improving efficiency of assisted reproduction technologies (ARTs).

developmental biology↗