scholarly journals Comprehensive Transcriptomic Analysis of Mouse Gonadal Development Involving Sexual Differentiation, Meiosis and Gametogenesis

2019 ◽  
Vol 21 (1) ◽  
Author(s):  
Jian Wang ◽  
Geng G. Tian ◽  
Zhuxia Zheng ◽  
Bo Li ◽  
Qinghe Xing ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Candidate Genes ◽  
Sexual Differentiation ◽  
Molecular Mechanisms ◽  
Expression Patterns ◽  
Global Gene Expression ◽  
Gonadal Development ◽  
Transcriptome Database ◽  
Alternatively Spliced ◽  
Expression Module

Abstract Background Mammalian gonadal development is crucial for fertility. Sexual differentiation, meiosis and gametogenesis are critical events in the process of gonadal development. Abnormalities in any of these events may cause infertility. However, owing to the complexity of these developmental events, the underlying molecular mechanisms are not fully understood and require further research. Results In this study, we employed RNA sequencing to examine transcriptome profiles of murine female and male gonads at crucial stages of these developmental events. By bioinformatics analysis, we identified a group of candidate genes that may participate in sexual differentiation, including Erbb3, Erbb4, and Prkg2. One hundred and two and 134 candidate genes that may be important for female and male gonadal development, respectively, were screened by analyzing the global gene expression patterns of developing female and male gonads. Weighted gene co-expression network analysis was performed on developing female gonads, and we identified a gene co-expression module related to meiosis. By alternative splicing analysis, we found that cassette-type exon and alternative start sites were the main forms of alternative splicing in developing gonads. A considerable portion of differentially expressed and alternatively spliced genes were involved in meiosis. Conclusion Taken together, our findings have enriched the gonadal transcriptome database and provided novel candidate genes and avenues to research the molecular mechanisms of sexual differentiation, meiosis, and gametogenesis.

scholarly journals Alternative Splicing of Transcription Factors' Genes: Beyond the Increase of Proteome Diversity

2009 ◽  
Vol 2009 ◽  
pp. 1-6 ◽  
Author(s):  
David Talavera ◽  
Modesto Orozco ◽  
Xavier de la Cruz
Keyword(s):  
Transcription Factors ◽  
Alternative Splicing ◽  
Expression Patterns ◽  
Developmental Changes ◽  
Functional Families ◽  
Transcription Regulators ◽  
Alternatively Spliced ◽  
The Impact ◽  
Human And Mouse

Functional modification of transcription regulators may lead to developmental changes and phenotypical differences between species. In this work, we study the influence of alternative splicing on transcription factors in human and mouse. Our results show that the impact of alternative splicing on transcription factors is similar in both species, meaning that the ways to increase variability should also be similar. However, when looking at the expression patterns of transcription factors, we observe that they tend to diverge regardless of the role of alternative splicing. Finally, we hypothesise that transcription regulation of alternatively spliced transcription factors could play an important role in the phenotypical differences between species, without discarding other phenomena or functional families.

scholarly journals Multi-level regulation of PKCδI alternative splicing by lithium chloride

2020 ◽  
Author(s):  
Deena Bader ◽  
Rekha S. Patel ◽  
Ashley Lui ◽  
Chetna Thawani ◽  
Rea Rupani ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Lithium Chloride ◽  
Noncoding Rna ◽  
Molecular Mechanisms ◽  
Fine Tuning ◽  
Serine Threonine Kinase ◽  
Rna Immunoprecipitation ◽  
Alternatively Spliced ◽  
Licl Treatment ◽  
Lncrna Neat1

Lithium chloride (LiCl) is commonly used in treatment of mood disorders, however its usage leads to weight gain which promotes metabolic disorders. Protein Kinase C delta (PKCδ), a serine/threonine kinase, is alternatively spliced to PKCδI and PKCδII in 3T3L1 cells. We previously demonstrated that PKCδI is the predominantly expressed isoform in 3T3L1 pre-adipocytes. Here, we demonstrate that LiCl treatment decreases PKCδI levels, increases formation of lipid droplets and increases oxidative stress. Hence, we investigated the molecular mechanisms underlying the regulation of PKCδI alternative splicing by LiCl. We previously demonstrated that the splice factor SFRS10 is essential for PKCδI splicing. Our results demonstrate that GSK3ß phosphorylates SFRS10 and SFRS10 is in a complex with long noncoding RNA NEAT1 to promote PKCδI splicing. Using PKCδ splicing minigene and RNA-immunoprecipitation assays, our results demonstrate that upon LiCl treatment, NEAT1 levels are reduced, GSK3ß activity is inhibited and SFRS10 phosphorylation is decreased which leads to decreased expression of PKCδI. Integration of the GSK3ß signaling pathway with the ribonucleoprotein complex of lncRNA NEAT1 and SFRS10 enables fine tuning of PKCδI expression during adipogenesis. Knowledge of the molecular pathways impacted by LiCl provide an understanding of the ascent of obesity as a comorbidity in disease management.

scholarly journals Genomic architecture of biomass heterosis inArabidopsis

2017 ◽  
Vol 114 (30) ◽  
pp. 8101-8106 ◽  
Author(s):  
Mei Yang ◽  
Xuncheng Wang ◽  
Diqiu Ren ◽  
Hao Huang ◽  
Miqi Xu ◽  
...  
Keyword(s):  
Candidate Genes ◽  
Molecular Mechanisms ◽  
Association Studies ◽  
Expression Patterns ◽  
Natural Populations ◽  
Genome Wide Association Studies ◽  
Genomic Architecture ◽  
Genome Wide ◽  
Stimulus Responsive ◽  
Abiotic Stimuli

Heterosis is most frequently manifested by the substantially increased vigorous growth of hybrids compared with their parents. Investigating genomic variations in natural populations is essential to understand the initial molecular mechanisms underlying heterosis in plants. Here, we characterized the genomic architecture associated with biomass heterosis in 200Arabidopsishybrids. The genome-wide heterozygosity of hybrids makes a limited contribution to biomass heterosis, and no locus shows an obvious overdominance effect in hybrids. However, the accumulation of significant genetic loci identified in genome-wide association studies (GWAS) in hybrids strongly correlates with better-parent heterosis (BPH). Candidate genes for biomass BPH fall into diverse biological functions, including cellular, metabolic, and developmental processes and stimulus-responsive pathways. Important heterosis candidates includeWUSCHEL,ARGOS, and some genes that encode key factors involved in cell cycle regulation. Interestingly, transcriptomic analyses in representativeArabidopsishybrid combinations reveal that heterosis candidate genes are functionally enriched in stimulus-responsive pathways, including responses to biotic and abiotic stimuli and immune responses. In addition, stimulus-responsive genes are repressed to low-parent levels in hybrids with high BPH, whereas middle-parent expression patterns are exhibited in hybrids with no BPH. Our study reveals a genomic architecture for understanding the molecular mechanisms of biomass heterosis inArabidopsis, in which the accumulation of the superior alleles of genes involved in metabolic and cellular processes improve the development and growth of hybrids, whereas the overall repressed expression of stimulus-responsive genes prioritizes growth over responding to environmental stimuli in hybrids under normal conditions.

scholarly journals Posttranscriptional Regulation of Splicing Factor SRSF1 and Its Role in Cancer Cell Biology

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Vânia Gonçalves ◽  
Peter Jordan
Keyword(s):  
Alternative Splicing ◽  
Cancer Cell ◽  
Cell Biology ◽  
Molecular Mechanisms ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Current Knowledge ◽  
Expression Patterns ◽  
Regulatory Protein ◽  
Gene Transcript

Over the past decade, alternative splicing has been progressively recognized as a major mechanism regulating gene expression patterns in different tissues and disease states through the generation of multiple mRNAs from the same gene transcript. This process requires the joining of selected exons or usage of different pairs of splice sites and is regulated by gene-specific combinations of RNA-binding proteins. One archetypical splicing regulator is SRSF1, for which we review the molecular mechanisms and posttranscriptional modifications involved in its life cycle. These include alternative splicing of SRSF1 itself, regulatory protein phosphorylation events, and the role of nuclear versus cytoplasmic SRSF1 localization. In addition, we resume current knowledge on deregulated SRSF1 expression in tumors and describe SRSF1-regulated alternative transcripts with functional consequences for cancer cell biology at different stages of tumor development.

scholarly journals Functional genomic analysis of corals from natural CO2-seeps reveals core molecular responses involved in acclimatization to ocean acidification

2017 ◽  
Author(s):  
CD Kenkel ◽  
A Moya ◽  
J Strahl ◽  
C Humphrey ◽  
LK Bay
Keyword(s):  
Climate Change ◽  
Ocean Acidification ◽  
Molecular Mechanisms ◽  
Expression Patterns ◽  
Genomic Analysis ◽  
Global Gene Expression ◽  
Specific Response ◽  
Coral Host ◽  
Functional Genomic Analysis ◽  
Response Capacity

ABSTRACTLittle is known about the potential for acclimatization or adaptation of corals to ocean acidification and even less about the molecular mechanisms underpinning these processes. Here we examine global gene expression patterns in corals and their intracellular algal symbionts from two replicate population pairs in Papua New Guinea that have undergone long-term acclimatization to natural variation in pCO2. In the coral host, only 61 genes were differentially expressed in response to pCO2environment, but the pattern of change was highly consistent between replicate populations, likely reflecting the core expression homeostasis response to ocean acidification. Functional annotations highlight lipid metabolism and a change in the stress response capacity of corals as a key part of this process. Specifically, constitutive downregulation of molecular chaperones was observed, which may impact response to combined climate-change related stressors. Elevated CO2has been hypothesized to benefit photosynthetic organisms but expression changes ofin hospite Symbiodiniumin response to acidification were greater and less consistent among reef populations. This population-specific response suggests hosts may need to adapt not only to an acidified environment, but also to changes in theirSymbiodiniumpopulations that may not be consistent among environments. This process adds another challenging dimension to the physiological process of coping with climate change.

scholarly journals Evolutionary conservation of the structure and expression of alternatively spliced Ultrabithorax isoforms from Drosophila.

Genetics ◽  
1994 ◽  
Vol 136 (3) ◽  
pp. 965-977
Author(s):  
H M Bomze ◽  
A J López
Keyword(s):  
Alternative Splicing ◽  
Protein Function ◽  
Developmental Regulation ◽  
Expression Patterns ◽  
Proximal Region ◽  
Amino Acid Sequences ◽  
Drosophila Virilis ◽  
Protein Isoforms ◽  
Developmentally Regulated ◽  
Alternatively Spliced

Abstract In Drosophila melanogaster, alternatively spliced mRNAs from the homeotic gene Ultrabithorax (Ubx) encode a family of structurally distinct homeoprotein isoforms. The developmentally regulated expression patterns of these isoforms suggest that they have specialized stage- and tissue-specific functions. To evaluate the functional importance of UBX isoform diversity and gain clues to the mechanism that regulates processing of Ubx RNAs, we have investigated whether the Ubx RNAs of other insects undergo similar alternative splicing. We have isolated and characterized Ubx cDNA fragments from D. melanogaster, Drosophila pseudoobscura, Drosophila hydei and Drosophila virilis, species separated by as much as 60 million years of evolution, and have found that three aspects of Ubx RNA processing have been conserved. (1) These four species exhibit identical patterns of optional exon use in a region adjacent to the homeodomain. (2) These four species produce the same family of UBX protein isoforms with identical amino acid sequences in the optional exons, even though the common amino-proximal region has undergone substantial divergence. The nucleotide sequences of the optional exons, including third positions of rare codons, have also been conserved strongly, suggesting functional constraints that are not limited to coding potential. (3) The tissue- and stage-specific patterns of expression of different UBX isoforms are identical among these Drosophila species, indicating that the developmental regulation of the alternative splicing events has also been conserved. These findings argue for an important role of alternative splicing in Ubx function. We discuss the implications of these results for models of UBX protein function and the mechanism of alternative splicing.

Alterations of Cell Signaling Pathways in Pediatric B-ALL Patients.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4427-4427
Author(s):  
Benedetta Accordi ◽  
Virginia Espina ◽  
Gertruuy te Kronnie ◽  
Lance A. Liotta ◽  
Emanuel F. Petricoin ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Drug Targets ◽  
Molecular Mechanisms ◽  
Lymphoblastic Leukemia ◽  
Cell Cycle Control ◽  
Expression Patterns ◽  
Global Gene Expression ◽  
Molecular Networks ◽  
Current Therapy ◽  
Kinase Substrates

Abstract The outcome for children with Acute Lymphoblastic Leukemia (ALL) has improved in the last few decades with current therapy resulting in an event free survival exceeding 75%. Despite of this, 25% of patients still relapse or resist to conventional therapies. Proteomics, in particular the Reverse Phase Protein Arrays (RPA), offers a new approach to study both the potential molecular mechanisms of drugs chemosensitivity versus resistance, and identify new drug targets in the patients that do not respond to therapy. RPA, which can quantitatively measure dozens to hundreds of phosphorylated kinase substrates from only a few thousand cells, can be used to profile the working state of cellular signaling pathways in a manner not possible with gene microarrays, since post-translational modifications cannot be accurately portrayed by global gene expression patterns alone. We employed RPA to study the phosphorylated cellular pathways in bone marrow aspirate samples collected prior to treatment. The phosphorylation status of 95 key signaling proteins, including pro-survival, pro-apoptotic and those involved in cell cycle control were analyzed from 120 pediatric B-ALL specimens collected at the Pediatric Oncohematology Laboratory (University of Padova) over the past 15 years. Molecular network analysis and phosphoprotein profiling were performed using commercially available software. Our results indicate that there may be a difference between the molecular networks of activated kinase substrates within leukemic patients depending on disease state, genotype, or response therapy. The discovery of the molecular mechanisms related to drug resistance could play an important role for individualizing therapy and may reveal new strategies to improve treatment outcome.

scholarly journals Changes in Ovary Transcriptome and Alternative splicing at estrus from Xiang pigs with Large and Small Litter Size

2019 ◽  
Author(s):  
Fuping Zhang ◽  
Liangting Tang ◽  
Xueqin Ran ◽  
Ning Mao ◽  
Yiqi Ruan ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Candidate Genes ◽  
Differentially Expressed Genes ◽  
Litter Size ◽  
Molecular Mechanisms ◽  
Reproductive Traits ◽  
Differentially Expressed ◽  
Rna Seq ◽  
Small Litter ◽  
Small Litter Size

AbstractBackground/AimsLitter size is one of the most important reproductive traits in pig breeding, which is affected by multiple genes and the environment. Ovaries are the most important reproductive organs and have a profound impact on the reproduction efficiency. Therefore, genetic differences in the ovaries may contribute to the observed differences in litter size. Although QTLs and candidate genes have been reported to affect the litter size in many pig breeds, however, the findings cannot elucidate the marked differences of the reproductive traits between breeds. The aim of present work is to elucidate the mechanisms of the differences for the reproductive traits and identify candidate genes associated with litter size in Xiang pig breed.MethodsThe changes in ovary transcriptome and alternative splicing were investigated at estrus between Xiang pigs with large and small litter size by RNA-seq technology. The RNA-seq results were confirmed by RT-qPCR method.ResultsWe detected 16,219 - 16,285 expressed genes and 12 types of alternative splicing (AS) events in Xiang pig samples. A total of 762 differentially expressed genes were identified by XL (Xiang pig group with larger litter size) vs XS (Xiang pig group with small litter size) sample comparisons. A total of 34 genes were upregulated and 728 genes were downregulated in XL ovary samples compared with the XS samples. Alternative splicing (AS) rates in XL samples were slightly lower than that observed in XS samples. Most of differentially expressed genes were differentially regulated on AS level. Eleven candidate genes were potentially identified to be related to Xiang pig fecundity and litter size, which may be closely related to the gonad development, oocyte maturation or embryo quality.ConclusionThe significant changes in the expression of the protein-coding genes and the level of alternative splicing in estrus ovarian transcriptome between XL and XS groups probably are the molecular mechanisms of phenotypic variation in litter size.

scholarly journals Hemimetabolous insects elucidate the origin of sexual development via alternative splicing

2019 ◽  
Author(s):  
Judith Wexler ◽  
Emily K. Delaney ◽  
Xavier Belles ◽  
Coby Schal ◽  
Ayako Wada-Katsumata ◽  
...  
Keyword(s):  
Sexual Development ◽  
Sexual Differentiation ◽  
Rna Splicing ◽  
Molecular Mechanisms ◽  
Protein Isoforms ◽  
Splicing Factor ◽  
Specific Expression ◽  
Male And Female ◽  
Pediculus Humanus ◽  
Alternatively Spliced

ABSTRACTInsects are the only animals in which sexual differentiation is controlled by sex-specific RNA splicing. Thedoublesex(dsx) transcription factor produces distinct male and female protein isoforms (DsxM and DsxF) under the control of the RNA splicing factortransformer(tra).traitself is also alternatively spliced so that a functional Tra protein is only present in females; thus, DsxM is produced by default, while DsxF expression requires Tra. The sex-specific Dsx isoforms are essential for both male and female sexual differentiation. This pathway is profoundly different from the molecular mechanisms that control sex-specific development in other animal groups. In animals as different as vertebrates, nematodes, and crustaceans, sexual differentiation involves male-specific transcription ofdsx-related transcription factors that are not alternatively spliced and play no role in female sexual development. To understand how the unique splicing-based mode of sexual differentiation found in insects evolved from a more ancestral transcription-based mechanism, we examineddsxandtraexpression in three basal, hemimetabolous insect orders. We find that functional Tra protein is limited to females in the kissing bugRhodnius prolixus(Hemiptera), but is present in both sexes in the lousePediculus humanus(Phthiraptera) and the cockroachBlattella germanica(Blattodea). Although alternatively spliceddsxisoforms are seen in all these insects, they are sex-specific in the cockroach and the kissing bug but not in the louse. InB. germanica, RNAi experiments show thatdsxis necessary for male, but not female, sexual differentiation, whiletracontrols female development via adsx-independent pathway. Our results suggest that the distinctive insect mechanism based on thetra-dsxsplicing cascade evolved in a gradual, mosaic process: sex-specific splicing ofdsxpredates its role in female sexual differentiation, while the role oftrain regulatingdsxsplicing and in sexual development more generally predates sex-specific expression of the Tra protein. We present a model where the canonicaltra-dsxaxis originated via merger between expandingdsxfunction (from males to both sexes) and narrowingtrafunction (from a general splicing factor to the dedicated regulator ofdsx).

scholarly journals Transcriptome analysis reveals the molecular mechanisms of heterosis on thermal resistance in hybrid abalone

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Qizhen Xiao ◽  
Zekun Huang ◽  
Yawei Shen ◽  
Yang Gan ◽  
Yi Wang ◽  
...  
Keyword(s):  
Heat Stress ◽  
Alternative Splicing ◽  
Thermal Resistance ◽  
Molecular Mechanisms ◽  
Southern China ◽  
Expression Patterns ◽  
Pathway Enrichment Analysis ◽  
High Survival ◽  
Genetic Characteristics ◽  
Alternative Splicing Events

Abstract Background Heterosis has been exploited for decades in different animals and crops due to it resulting in dramatic increases in yield and adaptability. Hybridization is a classical breeding method that can effectively improve the genetic characteristics of organisms through heterosis. Abalone has become an increasingly economically important aquaculture resource with high commercial value. However, due to changing climate, abalone is now facing serious threats of high temperature in summer. Interspecific hybrid abalone (Haliotis gigantea ♀ × H. discus hannai ♂, SD) has been cultured at large scale in southern China and has been shown high survival rates under heat stress in summer. Therefore, SD has become a good model material for heterosis research, but the molecular basis of heterosis remains elusive. Results Heterosis in thermal tolerance of SD was verified through Arrhenius break temperatures (ABT) of cardiac performance in this study. Then RNA-Sequencing was conducted to obtain gene expression patterns and alternative splicing events at control temperature (20 °C) and heat stress temperature (30 °C). A total of 356 (317 genes), 476 (435genes), and 876 (726 genes) significantly diverged alternative splicing events were identified in H. discus hannai (DD), H. gigantea (SS), and SD in response to heat stress, respectively. In the heat stress groups, 93.37% (20,512 of 21,969) of the expressed genes showed non-additive expression patterns, and over-dominance expression patterns of genes account for the highest proportion (40.15%). KEGG pathway enrichment analysis showed that the overlapping genes among common DEGs and NAGs were significantly enriched in protein processing in the endoplasmic reticulum, mitophagy, and NF-κB signaling pathway. In addition, we found that among these overlap genes, 39 genes had undergone alternative splicing events in SD. These pathways and genes may play an important role in the thermal resistance of hybrid abalone. Conclusion More alternative splicing events and non-additive expressed genes were detected in hybrid under heat stress and this may contribute to its thermal heterosis. These results might provide clues as to how hybrid abalone has a better physiological regulation ability than its parents under heat stress, to increase our understanding of heterosis in abalone.

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