Physiologically relevant miRNAs in mammalian oocytes are rare and highly abundant

Kataruka, Shubhangini; Kinterová, Veronika; Horvat, Filip; Kulmann, Marcos Iuri Roos; Kaňka, Jiří; Svoboda, Petr

doi:10.15252/embr.202153514

Cited by 5 publications

(1 citation statement)

References 80 publications

(126 reference statements)

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“…While it may be beneficial for cells to combine both nuclear (transcriptional) and cytosolic (post-transcriptional) machineries to achieve the desired goal of stabilizing intermediate states, the post-transcriptional mechanism may be advantageous in terms of avoiding some sources of noise. This is because transcription is subject to significant noise levels due to the low numbers of DNA coding for the regulatory products, whereas post-transcriptional mechanisms involve larger numbers of molecules ( Kataruka et al., 2022 ), which reduce intrinsic noise. Therefore, we expect that the proposed RNA-centric mechanism for stabilizing intermediate EMT states can be an efficient strategy for cells to adopt hybrid phenotypes with cytosolic reactions without the need for transcriptional regulatory systems.…”

Section: Discussionmentioning

confidence: 99%

Cooperative RNA degradation stabilizes intermediate epithelial-mesenchymal states and supports a phenotypic continuum

Nordick

Park

Quaranta³

et al. 2022

iScience

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Section: Discussionmentioning

confidence: 99%

Cooperative RNA degradation stabilizes intermediate epithelial-mesenchymal states and supports a phenotypic continuum

Nordick

Park

Quaranta³

et al. 2022

iScience

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Isolation, characterization, proteome, miRNAome, and the embryotrophic effects of chicken egg yolk nanovesicles (vitellovesicles)

Saadeldin

Tanga

Bang

et al. 2023

Sci Rep

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Egg yolk constitutes about a third of the structure of the chicken egg however, the molecular structure and physiological effects of egg yolk-derived lipid membranous vesicles are not clearly understood. In this study, for the first record, the egg yolk nanovesicles (vitellovesicles, VVs) were isolated, characterized, and used as a supplement for porcine embryo culture. Yolks of ten freshly oviposited eggs were filtered and ultracentrifuged at 100,000 × g for 3 h to obtain a pellet. Cryogenic transmission electron microscopy and nanoparticle tracking analysis of the pellet revealed bilipid membranous vesicles. Protein contents of the pellet were analyzed using tandem mass spectrometry and the miRNA content was also profiled through BGISEQ-500 sequencer. VVs were supplemented with the in vitro culture medium of day-7 hatched parthenogenetic blastocysts. After 2 days of blastocyst culture, the embryonic cell count was increased in VVs supplemented embryos in comparison to the non-supplemented embryos. TUNEL assay showed that apoptotic cells were increased in control groups when compared with the VVs supplemented group. Reduced glutathione was increased by 2.5 folds in the VVs supplemented group while reactive oxygen species were increased by 5.3 folds in control groups. Quantitative PCR analysis showed that VVs significantly increased the expression of lipid metabolism-associated genes (monoglyceride lipase and lipase E), anti-apoptotic gene (BCL2), and superoxide dismutase, while significantly reducing apoptotic gene (BAX). Culturing embryos on Matrigel basement membrane matrix indicated that VVs significantly enhanced embryo attachment and embryonic stem cell outgrowths compared to the non-supplemented group. This considers the first report to characterize the molecular bioactive cargo contents of egg yolk nanovesicles to show their embryotrophic effect on mammalian embryos. This effect might be attributed to the protein and miRNA cargo contents of VVs. VVs can be used for the formulation of in vitro culture medium for mammalian embryos including humans.

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Cooperative RNA degradation stabilizes intermediate epithelial-mesenchymal states and supports a phenotypic continuum

Nordick

Park

Quaranta

et al. 2022

Preprint

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Epithelial-mesenchymal transition (EMT) is a change in cell shape and mobility that supports development and cancer metastasis. Multiple intermediate EMT states reflecting hybrid epithelial and mesenchymal phenotypes were observed in various physiological and pathological conditions. Previous theoretical models explaining the intermediate EMT states rely on multiple regulatory loops involving transcriptional feedback, and these models produced three or four attractors with a given set of rate constants, which is incompatible with experimentally observed non-genetic heterogeneity reflecting a continuum-like EMT spectrum. EMT is regulated by many microRNAs that typically bind transcripts of EMT-related genes via multiple binding sites. It was unclear whether post-transcriptional regulations associated with the microRNA binding sites alone can stabilize intermediate EMT states. Here, we used models describing the post-transcriptional regulations with elementary reaction networks, finding that cooperative RNA degradation via multiple microRNA binding sites can generate four-attractor systems without transcriptional feedback. We identified many specific, experimentally supported instances of network structures predicted to permit intermediate EMT states. Furthermore, transcriptional feedback and the newly identified intermediates-enabling circuits can be combined to produce even more intermediate EMT states in both modular and emergent manners. Finally, multisite-mediated cooperative RNA degradation can increase the distribution of gene expression in the EMT spectrum and support the phenotypic continuum without the need of higher noise. Our work reveals a previously unknown possible role of cooperative RNA degradation and microRNA in EMT, providing a theoretical framework that can help to bridge the gap between mechanistic models and single-cell experiments.

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Physiologically relevant miRNAs in mammalian oocytes are rare and highly abundant

Cited by 5 publications

References 80 publications

Cooperative RNA degradation stabilizes intermediate epithelial-mesenchymal states and supports a phenotypic continuum

Cooperative RNA degradation stabilizes intermediate epithelial-mesenchymal states and supports a phenotypic continuum

Isolation, characterization, proteome, miRNAome, and the embryotrophic effects of chicken egg yolk nanovesicles (vitellovesicles)

Cooperative RNA degradation stabilizes intermediate epithelial-mesenchymal states and supports a phenotypic continuum

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