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Annual Review of Genetics Nov 2023The raison d'être of meiosis is shuffling of genetic information via Mendelian segregation and, within individual chromosomes, by DNA crossing-over. These outcomes are... (Review)
Review
The raison d'être of meiosis is shuffling of genetic information via Mendelian segregation and, within individual chromosomes, by DNA crossing-over. These outcomes are enabled by a complex cellular program in which interactions between homologous chromosomes play a central role. We first provide a background regarding the basic principles of this program. We then summarize the current understanding of the DNA events of recombination and of three processes that involve whole chromosomes: homolog pairing, crossover interference, and chiasma maturation. All of these processes are implemented by direct physical interaction of recombination complexes with underlying chromosome structures. Finally, we present convergent lines of evidence that the meiotic program may have evolved by coupling of this interaction to late-stage mitotic chromosome morphogenesis.
Topics: Chromosome Pairing; Meiosis; Chromosomes; DNA; Chromosome Segregation; Crossing Over, Genetic
PubMed: 37788458
DOI: 10.1146/annurev-genet-061323-044915 -
Nature Nov 2023Reproductive isolation occurs when the genomes of two populations accumulate genetic incompatibilities that prevent interbreeding. Understanding of hybrid...
Reproductive isolation occurs when the genomes of two populations accumulate genetic incompatibilities that prevent interbreeding. Understanding of hybrid incompatibility at the cell biology level is limited, particularly in the case of hybrid female sterility. Here we find that species divergence in condensin regulation and centromere organization between two mouse species, Mus musculus domesticus and Mus spretus, drives chromosome decondensation and mis-segregation in their F hybrid oocytes, reducing female fertility. The decondensation in hybrid oocytes was especially prominent at pericentromeric major satellites, which are highly abundant at M. m. domesticus centromeres, leading to species-specific chromosome mis-segregation and egg aneuploidy. Consistent with the condensation defects, a chromosome structure protein complex, condensin II, was reduced on hybrid oocyte chromosomes. We find that the condensin II subunit NCAPG2 was specifically reduced in the nucleus in prophase and that overexpressing NCAPG2 rescued both the decondensation and egg aneuploidy phenotypes. In addition to the overall reduction in condensin II on chromosomes, major satellites further reduced condensin II levels locally, explaining why this region is particularly prone to decondensation. Together, this study provides cell biological insights into hybrid incompatibility in female meiosis and demonstrates that condensin misregulation and pericentromeric satellite expansion can establish a reproductive isolating barrier in mammals.
Topics: Animals; Female; Mice; Adenosine Triphosphatases; Aneuploidy; Centromere; Chromosome Segregation; Chromosomes, Mammalian; DNA-Binding Proteins; Hybridization, Genetic; Infertility, Female; Meiosis; Multiprotein Complexes; Oocytes; Prophase; Cell Nucleus
PubMed: 37914934
DOI: 10.1038/s41586-023-06700-6 -
Trends in Parasitology Oct 2023Meiosis is sexual cell division, a process in eukaryotes whereby haploid gametes are produced. Compared to canonical model eukaryotes, meiosis in apicomplexan parasites... (Review)
Review
Meiosis is sexual cell division, a process in eukaryotes whereby haploid gametes are produced. Compared to canonical model eukaryotes, meiosis in apicomplexan parasites appears to diverge from the process with respect to the molecular mechanisms involved; the biology of Plasmodium meiosis, and its regulation by means of post-translational modification, are largely unexplored. Here, we discuss the impact of technological advances in cell biology, evolutionary bioinformatics, and genome-wide functional studies on our understanding of meiosis in the Apicomplexa. These parasites, including Plasmodium falciparum, Toxoplasma gondii, and Eimeria spp., have significant socioeconomic impact on human and animal health. Understanding this key stage during the parasite's life cycle may well reveal attractive targets for therapeutic intervention.
Topics: Animals; Humans; Plasmodium; Eukaryota; Plasmodium falciparum; Meiosis; Toxoplasma
PubMed: 37541799
DOI: 10.1016/j.pt.2023.07.002 -
Nature Communications Oct 2023N-methyladenosine (mA) maintains maternal RNA stability in oocytes. One regulator of mA, ALKBH5, reverses mA deposition and is essential in RNA metabolism. However, the...
N-methyladenosine (mA) maintains maternal RNA stability in oocytes. One regulator of mA, ALKBH5, reverses mA deposition and is essential in RNA metabolism. However, the specific role of ALKBH5 in oocyte maturation remains elusive. Here, we show that Alkbh5 depletion causes a wide range of defects in oocyte meiosis and results in female infertility. Temporal profiling of the maternal transcriptomes revealed striking RNA accumulation in Alkbh5 oocytes during meiotic maturation. Analysis of mA dynamics demonstrated that ALKBH5-mediated mA demethylation ensures the timely degradation of maternal RNAs, which is severely disrupted following Alkbh5 depletion. A distinct subset of transcripts with persistent mA peaks are recognized by the mA reader IGF2BP2 and thus remain stabilized, resulting in impaired RNA clearance. Additionally, reducing IGF2BP2 in Alkbh5-depleted oocytes partially rescued these defects. Overall, this work identifies ALKBH5 as a key determinant of oocyte quality and unveil the facilitating role of ALKBH5-mediated mA removal in maternal RNA decay.
Topics: Female; Humans; AlkB Homolog 5, RNA Demethylase; Meiosis; Methylation; Oocytes; Oogenesis; RNA, Messenger; RNA-Binding Proteins
PubMed: 37848452
DOI: 10.1038/s41467-023-42302-6 -
Trends in Genetics : TIG Apr 2024Meiosis is essential for gamete production in all sexually reproducing organisms. It entails two successive cell divisions without DNA replication, producing haploid... (Review)
Review
Meiosis is essential for gamete production in all sexually reproducing organisms. It entails two successive cell divisions without DNA replication, producing haploid cells from diploid ones. This process involves complex morphological and molecular differentiation that varies across species and between sexes. Specialized genomic events like meiotic recombination and chromosome segregation are tightly regulated, including preparation for post-meiotic development. Research in model organisms, notably yeast, has shed light on the genetic and molecular aspects of meiosis and its regulation. Although mammalian meiosis research faces challenges, particularly in replicating gametogenesis in vitro, advances in genetic and genomic technologies are providing mechanistic insights. Here we review the genetics and molecular biology of meiotic gene expression control, focusing on mammals.
Topics: Animals; Meiosis; Saccharomyces cerevisiae; Gametogenesis; Chromosome Segregation; DNA Replication; Mammals
PubMed: 38177041
DOI: 10.1016/j.tig.2023.12.006 -
LSM14B is essential for oocyte meiotic maturation by regulating maternal mRNA storage and clearance.Nucleic Acids Research Nov 2023Fully grown oocytes remain transcriptionally quiescent, yet many maternal mRNAs are synthesized and retained in growing oocytes. We now know that maternal mRNAs are...
Fully grown oocytes remain transcriptionally quiescent, yet many maternal mRNAs are synthesized and retained in growing oocytes. We now know that maternal mRNAs are stored in a structure called the mitochondria-associated ribonucleoprotein domain (MARDO). However, the components and functions of MARDO remain elusive. Here, we found that LSM14B knockout prevents the proper storage and timely clearance of mRNAs (including Cyclin B1, Btg4 and other mRNAs that are translationally activated during meiotic maturation), specifically by disrupting MARDO assembly during oocyte growth and meiotic maturation. With decreased levels of storage and clearance, the LSM14B knockout oocytes failed to enter meiosis II, ultimately resulting in female infertility. Our results demonstrate the function of LSM14B in MARDO assembly, and couple the MARDO with mRNA clearance and oocyte meiotic maturation.
Topics: Female; Humans; Meiosis; Oocytes; Oogenesis; RNA, Messenger; RNA, Messenger, Stored; Mice, Inbred C57BL; Male; Animals; Mice
PubMed: 37889087
DOI: 10.1093/nar/gkad919 -
Advanced Science (Weinheim,... Sep 2023Abnormal resumption of meiosis and decreased oocyte quality are hallmarks of maternal aging. Transcriptional silencing makes translational control an urgent task during...
Abnormal resumption of meiosis and decreased oocyte quality are hallmarks of maternal aging. Transcriptional silencing makes translational control an urgent task during meiosis resumption in maternal aging. However, insights into aging-related translational characteristics and underlying mechanisms are limited. Here, using multi-omics analysis of oocytes, it is found that translatomics during aging is related to changes in the proteome and reveals decreased translational efficiency with aging phenotypes in mouse oocytes. Translational efficiency decrease is associated with the N6-methyladenosine (m6A) modification of transcripts. It is further clarified that m6A reader YTHDF3 is significantly decreased in aged oocytes, inhibiting oocyte meiotic maturation. YTHDF3 intervention perturbs the translatome of oocytes and suppress the translational efficiency of aging-associated maternal factors, such as Hells, to affect the oocyte maturation. Moreover, the translational landscape is profiled in human oocyte aging, and the similar translational changes of epigenetic modifications regulators between human and mice oocyte aging are observed. In particular, due to the translational silence of YTHDF3 in human oocytes, translation activity is not associated with m6A modification, but alternative splicing factor SRSF6. Together, the findings profile the specific translational landscapes during oocyte aging in mice and humans, and uncover non-conservative regulators on translation control in meiosis resumption and maternal aging.
Topics: Humans; Mice; Animals; Aged; Multiomics; Oocytes; Meiosis; Adenosine; Serine-Arginine Splicing Factors; Phosphoproteins
PubMed: 37401155
DOI: 10.1002/advs.202301538 -
Nature Cell Biology Oct 2023Human spermatogenesis is a highly ordered process; however, the roles of DNA methylation and chromatin accessibility in this process remain largely unknown. Here by...
Human spermatogenesis is a highly ordered process; however, the roles of DNA methylation and chromatin accessibility in this process remain largely unknown. Here by simultaneously investigating the chromatin accessibility, DNA methylome and transcriptome landscapes using the modified single-cell chromatin overall omic-scale landscape sequencing approach, we revealed that the transcriptional changes throughout human spermatogenesis were correlated with chromatin accessibility changes. In particular, we identified a set of transcription factors and cis elements with potential functions. A round of DNA demethylation was uncovered upon meiosis initiation in human spermatogenesis, which was associated with male meiotic recombination and conserved between human and mouse. Aberrant DNA hypermethylation could be detected in leptotene spermatocytes of certain nonobstructive azoospermia patients. Functionally, the intervention of DNA demethylation affected male meiotic recombination and fertility. Our work provides multi-omics landscapes of human spermatogenesis at single-cell resolution and offers insights into the association between DNA demethylation and male meiotic recombination.
Topics: Humans; Male; Animals; Mice; DNA Demethylation; Multiomics; Spermatogenesis; Meiosis; Chromatin
PubMed: 37723297
DOI: 10.1038/s41556-023-01232-7 -
Yi Chuan = Hereditas Dec 2023Normal oogenesis is crucial to successful reproduction. During the human female fetal stage, primordial germ cells transform from mitosis to meiosis. After synapsis and... (Review)
Review
Normal oogenesis is crucial to successful reproduction. During the human female fetal stage, primordial germ cells transform from mitosis to meiosis. After synapsis and recombination of homologous chromosomes, meiosis is arrested at the diplotene stage of prophase in meiosis I. The maintenance of oocyte meiotic arrest in the follicle is primarily attributed to high cytoplasmic concentrations of cyclic adenosine monophosphate. During the menstrual cycle, follicle-stimulating hormone and luteinizing hormone lead to the resumption of meiosis that occurs in certain oocytes and complete the ovulation process. Anything that disturbs oocyte meiosis may result in failure of oogenesis and seriously affect both the fertilization and embryonic development. The rapid development of the assisted reproduction technology, high-throughput sequencing technology, and molecular biology technology provide new ideas and means for human to understand molecular mechanism of meiosis and diagnosis and treatment of oocyte maturation defects. In this review, we mainly summarize the recent physiological and pathological mechanisms of oogenesis, involving homologous recombination, meiotic arrest and resumption, maternal mRNA degradation, post-translational regulation, zona pellucida assembly, and so on. We wish to take this opportunity to raise the awareness of researchers in related fields on oocyte meiosis, providing a theoretical basis for further research and disease treatments.
Topics: Meiosis; Oocytes; Humans; Female; Oogenesis; Animals
PubMed: 38764273
DOI: 10.16288/j.yczz.23-170