Regulation of translation is essential for the diverse biological processes involved in development. Particularly, mammalian oocyte development requires the precisely controlled translation of maternal transcripts to coordinate meiotic and early embryo progression while transcription is silent. It has been recently reported that key components of mRNA translation control are short and long noncoding RNAs (ncRNAs). We found that the ncRNABrain cytoplasmic 1 (BC1) has a role in the fully grown germinal vesicle (GV) mouse oocyte, where is highly expressed in the cytoplasm associated with polysomes. Overexpression of BC1 in GV oocyte leads to a minute decrease in global translation with a significant reduction of specific mRNA translation via interaction with the Fragile X Mental Retardation Protein (FMRP). BC1 performs a repressive role in translation only in the GV stage oocyte without forming FMRP or Poly(A) granules. In conclusion, BC1 acts as the translational repressor of specific mRNAs in the GV stage via its binding to a subset of mRNAs and physical interaction with FMRP. The results reported herein contribute to the understanding of the molecular mechanisms of developmental events connected with maternal mRNA translation.

• Keywords
• Non-coding RNA, development, embryo, oocyte, translation,
• MeSH
• Cytoplasm genetics   metabolism   MeSH
• Mice, Inbred ICR MeSH
• Mice MeSH
• RNA, Untranslated genetics   MeSH
• Oocytes cytology   physiology   MeSH
• Oogenesis * MeSH
• Polyribosomes genetics   metabolism   MeSH
• Protein Biosynthesis * MeSH
• RNA, Small Cytoplasmic genetics   MeSH
• Animals MeSH
• Check Tag
• Mice MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• RNA, Untranslated MeSH
• RNA, Small Cytoplasmic MeSH

MicroRNAs (miRNAs) are ubiquitous small RNAs guiding post-transcriptional gene repression in countless biological processes. However, the miRNA pathway in mouse oocytes appears inactive and dispensable for development. We propose that marginalization of the miRNA pathway activity stems from the constraints and adaptations of RNA metabolism elicited by the diluting effects of oocyte growth. We report that miRNAs do not accumulate like mRNAs during the oocyte growth because miRNA turnover has not adapted to it. The most abundant miRNAs total tens of thousands of molecules in growing (∅ 40 μm) and fully grown (∅ 80 μm) oocytes, a number similar to that observed in much smaller fibroblasts. The lack of miRNA accumulation results in a 100-fold lower miRNA concentration in fully grown oocytes than in somatic cells. This brings a knock-down-like effect, where diluted miRNAs engage targets but are not abundant enough for significant repression. Low-miRNA concentrations were observed in rat, hamster, porcine and bovine oocytes, arguing that miRNA inactivity is not mouse-specific but a common mammalian oocyte feature. Injection of 250,000 miRNA molecules was sufficient to restore reporter repression in mouse and porcine oocytes, suggesting that miRNA inactivity comes from low-miRNA abundance and not from some suppressor of the pathway.

• MeSH
• 3T3 Cells MeSH
• Species Specificity MeSH
• Cricetinae MeSH
• Rats MeSH
• Cells, Cultured MeSH
• RNA, Messenger genetics   metabolism   MeSH
• MicroRNAs genetics   metabolism   MeSH
• Mice, Inbred C57BL MeSH
• Mice MeSH
• Oocytes cytology   metabolism   MeSH
• Oogenesis * MeSH
• Swine MeSH
• Cattle MeSH
• Models, Theoretical MeSH
• Gene Expression Regulation, Developmental MeSH
• Animals MeSH
• Check Tag
• Cricetinae MeSH
• Rats MeSH
• Mice MeSH
• Cattle MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• RNA, Messenger MeSH
• MicroRNAs MeSH

Tens of thousands of rapidly evolving long non-coding RNA (lncRNA) genes have been identified, but functions were assigned to relatively few of them. The lncRNA contribution to the mouse oocyte physiology remains unknown. We report the evolutionary history and functional analysis of Sirena1, the most expressed lncRNA and the 10th most abundant poly(A) transcript in mouse oocytes. Sirena1 appeared in the common ancestor of mouse and rat and became engaged in two different post-transcriptional regulations. First, antisense oriented Elob pseudogene insertion into Sirena1 exon 1 is a source of small RNAs targeting Elob mRNA via RNA interference. Second, Sirena1 evolved functional cytoplasmic polyadenylation elements, an unexpected feature borrowed from translation control of specific maternal mRNAs. Sirena1 knock-out does not affect fertility, but causes minor dysregulation of the maternal transcriptome. This includes increased levels of Elob and mitochondrial mRNAs. Mitochondria in Sirena1-/- oocytes disperse from the perinuclear compartment, but do not change in number or ultrastructure. Taken together, Sirena1 contributes to RNA interference and mitochondrial aggregation in mouse oocytes. Sirena1 exemplifies how lncRNAs stochastically engage or even repurpose molecular mechanisms during evolution. Simultaneously, Sirena1 expression levels and unique functional features contrast with the lack of functional importance assessed under laboratory conditions.

• MeSH
• Gene Knockout Techniques MeSH
• Rats MeSH
• RNA, Messenger genetics   MeSH
• Mitochondria genetics   ultrastructure   MeSH
• Mice MeSH
• Oocytes growth & development   metabolism   ultrastructure   MeSH
• Polyadenylation genetics   MeSH
• RNA, Long Noncoding genetics   MeSH
• RNA, Mitochondrial genetics   MeSH
• Transcriptome genetics   MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• RNA, Messenger MeSH
• mitochondrial messenger RNA MeSH Browser
• RNA, Long Noncoding MeSH
• RNA, Mitochondrial MeSH

The tight correlation between mRNA distribution and subsequent protein localization and function indicate a major role for mRNA localization within the cell. RNA localization, followed by local translation, presents a mechanism for spatial and temporal gene expression regulation utilized by various cell types. However, little is known about mRNA localization and translation in the mammalian oocyte and early embryo. Importantly, fully-grown oocyte becomes transcriptionally inactive and only utilizes transcripts previously synthesized and stored during earlier development. We discovered an abundant RNA population in the oocyte and early embryo nucleus together with RNA binding proteins. We also characterized specific ribosomal proteins, which contribute to translation in the oocyte and embryo. By applying selected markers to mouse and human oocytes, we found that there might be a similar mechanism of RNA metabolism in both species. In conclusion, we visualized the localization of RNAs and translation machinery in the oocyte, that could shed light on this terra incognita of these unique cell types in mouse and human.

• MeSH
• Embryo, Mammalian metabolism   ultrastructure   MeSH
• Cells, Cultured MeSH
• Humans MeSH
• RNA, Messenger analysis   genetics   MeSH
• Mice MeSH
• Oocytes metabolism   ultrastructure   MeSH
• RNA-Binding Proteins analysis   genetics   MeSH
• Protein Biosynthesis * MeSH
• Transcriptome MeSH
• Gene Expression Regulation, Developmental * MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Mice MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• RNA, Messenger MeSH
• RNA-Binding Proteins MeSH

The oocyte-to-embryo transition (OET) transforms a differentiated gamete into pluripotent blastomeres. The accompanying maternal-zygotic RNA exchange involves remodeling of the long non-coding RNA (lncRNA) pool. Here, we used next generation sequencing and de novo transcript assembly to define the core population of 1,600 lncRNAs expressed during the OET (lncRNAs). Relative to mRNAs, OET lncRNAs were less expressed and had shorter transcripts, mainly due to fewer exons and shorter 5' terminal exons. Approximately half of OET lncRNA promoters originated in retrotransposons suggesting their recent emergence. Except for a small group of ubiquitous lncRNAs, maternal and zygotic lncRNAs formed two distinct populations. The bulk of maternal lncRNAs was degraded before the zygotic genome activation. Interestingly, maternal lncRNAs seemed to undergo cytoplasmic polyadenylation observed for dormant mRNAs. We also identified lncRNAs giving rise to trans-acting short interfering RNAs, which represent a novel lncRNA category. Altogether, we defined the core OET lncRNA transcriptome and characterized its remodeling during early development. Our results are consistent with the notion that rapidly evolving lncRNAs constitute signatures of cells-of-origin while a minority plays an active role in control of gene expression across OET. Our data presented here provide an excellent source for further OET lncRNA studies.

• Keywords
• endo-siRNA, lncRNA, oocyte, polyadenylation, zygote,
• MeSH
• Blastomeres metabolism   MeSH
• Embryo, Mammalian metabolism   MeSH
• Mice MeSH
• Oocytes metabolism   MeSH
• RNA, Long Noncoding genetics   metabolism   MeSH
• Sequence Analysis, RNA MeSH
• Gene Expression Profiling MeSH
• High-Throughput Nucleotide Sequencing MeSH
• Gene Expression Regulation, Developmental * MeSH
• Animals MeSH
• Check Tag
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• RNA, Long Noncoding MeSH

The fully grown mammalian oocyte is transcriptionally quiescent and utilizes only transcripts synthesized and stored during early development. However, we find that an abundant RNA population is retained in the oocyte nucleus and contains specific mRNAs important for meiotic progression. Here we show that during the first meiotic division, shortly after nuclear envelope breakdown, translational hotspots develop in the chromosomal area and in a region that was previously surrounded the nucleus. These distinct translational hotspots are separated by endoplasmic reticulum and Lamin, and disappear following polar body extrusion. Chromosomal translational hotspots are controlled by the activity of the mTOR-eIF4F pathway. Here we reveal a mechanism that-following the resumption of meiosis-controls the temporal and spatial translation of a specific set of transcripts required for normal spindle assembly, chromosome alignment and segregation.

• MeSH
• Time Factors MeSH
• Down-Regulation MeSH
• Eukaryotic Initiation Factor-4F metabolism   MeSH
• Fertilization MeSH
• Nuclear Envelope metabolism   MeSH
• Humans MeSH
• Meiosis MeSH
• RNA, Messenger genetics   metabolism   MeSH
• Mice MeSH
• Genomic Instability MeSH
• Oocytes metabolism   MeSH
• Protein Biosynthesis * MeSH
• RNA Caps metabolism   MeSH
• Chromosomes, Mammalian metabolism   MeSH
• Mammals metabolism   MeSH
• Signal Transduction * MeSH
• TOR Serine-Threonine Kinases metabolism   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Eukaryotic Initiation Factor-4F MeSH
• RNA, Messenger MeSH
• RNA Caps MeSH
• TOR Serine-Threonine Kinases MeSH

At the end of the growth phase, mouse antral follicle oocytes acquire full developmental competence. In the mouse, this event is marked by the transition from the so-called non-surrounded nucleolus (NSN) chromatin configuration into the transcriptionally quiescent surrounded nucleolus (SN) configuration, which is named after a prominent perinucleolar condensed chromatin ring. However, the SN chromatin configuration alone is not sufficient for determining the developmental competence of the SN oocyte. There are additional nuclear and cytoplamic factors involved, while a little is known about the changes occurring in the cytoplasm during the NSN/SN transition. Here, we report functional analysis of maternal ELAVL2 an AU-rich element binding protein. Elavl2 gene encodes an oocyte-specific protein isoform (denoted ELAVL2°), which acts as a translational repressor. ELAVL2° is abundant in fully grown NSN oocytes, is ablated during the NSN/SN transition and remains low during the oocyte-to-embryo transition (OET). ELAVL2° overexpression during meiotic maturation causes errors in chromosome segregation, indicating the significance of naturally reduced ELAVL2° levels in SN oocytes. On the other hand, during oocyte growth, prematurely reduced Elavl2 expression results in lower yields of fully grown and meiotically matured oocytes, suggesting that Elavl2 is necessary for proper oocyte maturation. Moreover, Elavl2 knockdown showed stimulating effects on translation in fully grown oocytes. We propose that ELAVL2 has an ambivalent role in oocytes: it functions as a pleiotropic translational repressor in efficient production of fully grown oocytes, while its disposal during the NSN/SN transition contributes to the acquisition of full developmental competence.

• Keywords
• ARE, ELAVL2, NSN, SN, chromatin, oocyte,
• MeSH
• Cell Line MeSH
• ELAV-Like Protein 2 genetics   metabolism   MeSH
• Gene Knockdown Techniques MeSH
• Humans MeSH
• Meiosis physiology   MeSH
• Mice, Inbred BALB C MeSH
• Mice, Inbred C57BL MeSH
• Mice, Transgenic MeSH
• Oocytes cytology   metabolism   MeSH
• Ovarian Follicle cytology   metabolism   MeSH
• Protein Isoforms genetics   metabolism   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• ELAV-Like Protein 2 MeSH
• Elavl2 protein, mouse MeSH Browser
• Protein Isoforms MeSH

Processing bodies (P-bodies) are dynamic cytoplasmic structures involved in mRNA degradation, but the mechanism that governs their formation is poorly understood. In this paper, we address a role of Like-Sm (LSm) proteins in formation of P-bodies and provide evidence that depletion of nuclear LSm8 increases the number of P-bodies, while LSm8 overexpression leads to P-body loss. We show that LSm8 knockdown causes relocalization of LSm4 and LSm6 proteins to the cytoplasm and suggest that LSm8 controls nuclear accumulation of all LSm2-7 proteins. We propose a model in which redistribution of LSm2-7 to the cytoplasm creates new binding sites for other P-body components and nucleates new, microscopically visible structures. The model is supported by prolonged residence of two P-body proteins, DDX6 and Ago2, in P-bodies after LSm8 depletion, which indicates stronger interactions between these proteins and P-bodies. Finally, an increased number of P-bodies has negligible effects on microRNA-mediated translation repression and nonsense mediated decay, further supporting the view that the function of proteins localized in P-bodies is independent of visible P-bodies.

• MeSH
• Autoantigens metabolism   MeSH
• Cell Nucleus metabolism   MeSH
• Cytoplasmic Granules metabolism   MeSH
• DEAD-box RNA Helicases metabolism   MeSH
• Microscopy, Fluorescence MeSH
• Humans MeSH
• Ribonucleoprotein, U4-U6 Small Nuclear metabolism   physiology   MeSH
• N-Terminal Acetyltransferase C metabolism   physiology   MeSH
• RNA Processing, Post-Transcriptional * MeSH
• RNA-Binding Proteins metabolism   MeSH
• Proto-Oncogene Proteins metabolism   MeSH
• Recombinant Fusion Proteins metabolism   MeSH
• Ribonucleoproteins, Small Nuclear metabolism   MeSH
• Protein Transport MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Autoantigens MeSH
• DDX6 protein, human MeSH Browser
• DEAD-box RNA Helicases MeSH
• Ribonucleoprotein, U4-U6 Small Nuclear MeSH
• N-Terminal Acetyltransferase C MeSH
• NAA38 protein, human MeSH Browser
• RNA-Binding Proteins MeSH
• Proto-Oncogene Proteins MeSH
• Recombinant Fusion Proteins MeSH
• Ribonucleoproteins, Small Nuclear MeSH
• TNRC6A protein, human MeSH Browser

Small RNA molecules regulating gene expression received a status of omnipresent master regulators of eukaryotic lives with almost supernatural powers. Mammals hold at least three mechanisms employing small RNA molecules for regulating gene expression. One of these mechanisms, the microRNA (miRNA) pathway, involves currently over a thousand of genome-encoded different miRNAs that are claimed to extend their control over more than a half of a genome. Here, I discuss how and why mouse oocytes and early embryos ignore the regulatory power of miRNAs, adding another surprising feature to the field of small RNAs.

• MeSH
• Embryo, Mammalian metabolism   MeSH
• MicroRNAs genetics   MeSH
• Mice MeSH
• Oocytes metabolism   MeSH
• RNA Interference * MeSH
• RNA, Messenger, Stored MeSH
• Gene Expression Regulation, Developmental * MeSH
• Animals MeSH
• Check Tag
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• MicroRNAs MeSH
• RNA, Messenger, Stored MeSH

RNA silencing is a complex of mechanisms that regulate gene expression through small RNA molecules. The microRNA (miRNA) pathway is the most common of these in mammals. Genome-encoded miRNAs suppress translation in a sequence-specific manner and facilitate shifts in gene expression during developmental transitions. Here, we discuss the role of miRNAs in oocyte-to-zygote transition and in the control of pluripotency. Existing data suggest a common principle involving miRNAs in defining pluripotent and differentiated cells. RNA silencing pathways also rapidly evolve, resulting in many unique features of RNA silencing in different taxonomic groups. This is exemplified in the mouse model of oocyte-to-zygote transition, in which the endogenous RNA interference pathway has acquired a novel role in regulating protein-coding genes, while the miRNA pathway has become transiently suppressed.

• MeSH
• Phylogeny MeSH
• Humans MeSH
• RNA, Small Interfering genetics   metabolism   MeSH
• MicroRNAs classification   genetics   metabolism   MeSH
• Molecular Sequence Data MeSH
• Oocytes cytology   physiology   MeSH
• Pluripotent Stem Cells cytology   physiology   MeSH
• RNA Interference * MeSH
• Base Sequence MeSH
• Sequence Alignment MeSH
• Animals MeSH
• Zygote cytology   physiology   MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH
• Names of Substances
• RNA, Small Interfering MeSH
• MicroRNAs MeSH