scholarly journals Sex-dependent and -independent transcriptional changes during haploid phase gametogenesis in the sugar kelpSaccharina latissima

2019 ◽  
Author(s):  
Gareth A Pearson ◽  
Neusa Martins ◽  
Pedro Madeira ◽  
Ester A Serrão ◽  
Inka Bartsch
Keyword(s):  
Ribosome Biogenesis ◽  
Mitotic Cell ◽  
Saccharina Latissima ◽  
Independent Manner ◽  
Coordinate Gene Expression ◽  
Core Set ◽  
Transcriptional Changes ◽  
Genome Level ◽  
Male Specific ◽  
Rapid Activation

AbstractIn haplodiplontic lineages, sexual reproduction occurs in haploid parents without meiosis. Although widespread in multicellular lineages such as brown algae (Phaeophyceae), haplodiplontic gametogenesis has been little studied at the molecular level. We addressed this by generating an annotated reference transcriptome for the gametophytic phase of the sugar kelp,Saccharina latissima. Transcriptional profiles of microscopic male and female gametophytes were analysed at four time points during the transition from vegetative growth to gametogenesis. Gametogenic signals resulting from a switch in culture irradiance from red to white light activated a core set of genes in a sex-independent manner, involving rapid activation of ribosome biogenesis, transcription and translation related pathways, with several acting at the post-transcriptional or post-translational level. Additional genes regulating nutrient acquisition and key carbohydrate-energy pathways were also identified. Candidate sex-biased genes under gametogenic conditions had potentially key roles in controlling female- and male-specific gametogenesis. Among these were several sex-biased or - specific E3 ubiquitin-protein ligases that may have important regulatory roles. Females specifically expressed several genes that coordinate gene expression and/or protein degradation, and the synthesis of inositol-containing compounds. Other female-biased genes supported parallels with oogenesis in divergent multicellular lineages, in particular reactive oxygen signalling via an NADPH-oxidase. Males specifically expressed the hypothesised brown algal sex-determining factor. Male-biased expression mainly involved upregulation of genes that control mitotic cell proliferation and spermatogenesis in other systems, as well as multiple flagella-related genes. Our data and results enhance genome-level understanding of gametogenesis in this ecologically and economically important multicellular lineage.

scholarly journals Nonsense mediated RNA decay factor UPF1 is critical for post-transcriptional and translational gene regulation in Arabidopsis

2020 ◽  
Author(s):  
Vivek K. Raxwal ◽  
Craig G. Simpson ◽  
Jiradet Gloggnitzer ◽  
Juan Carlos Entinze ◽  
Wenbin Guo ◽  
...  
Keyword(s):  
Ribosome Biogenesis ◽  
Control Mechanism ◽  
Transcriptome Assembly ◽  
Regulation Of Gene Expression ◽  
Translational Repression ◽  
Rna Decay ◽  
Genome Wide ◽  
Mrna Variants ◽  
Nonsense Mediated Rna Decay ◽  
Rapid Activation

AbstractNonsense mediated RNA decay (NMD) is an evolutionary conserved RNA control mechanism that has also been implicated in the broader regulation of gene expression. Nevertheless, a role for NMD in genome regulation has not been fully assessed, partially because NMD inactivation is lethal in many organisms. Here, we performed in depth comparative analysis of Arabidopsis mutants lacking key proteins involved in different steps of NMD. We observed that UPF3, UPF1, and SMG7 have different impacts on NMD and the Arabidopsis transcriptome, with UPF1 having the biggest effect. Transcriptome assembly using stringent pipeline in UPF1-null plants revealed genome wide changes in alternative splicing, including switches in mRNA variants, suggesting a role for UPF1 in splicing. We further found that UPF1 inactivation leads to translational repression, manifested by a global shift in mRNAs from polysomes to monosomes and a downregulation of genes involved in translation and ribosome biogenesis. Despite this global change, NMD targets and low-expressed mRNAs with short half-lives were enriched in polysomes, indicating that UPF1 specifically suppresses the translation of aberrant RNAs. Particularly striking was an increase in the translation of TIR domain-containing, nucleotide-binding, leucine-rich repeat (TNL) immune receptors. The regulation of TNLs via UPF1/NMD-mediated mRNA stability and translational de-repression offers a dynamic mechanism for the rapid activation of TNLs in response to pathogen attack.

scholarly journals The Ribosome Biogenesis Factor Ltv1 Is Essential for Digestive Organ Development and Definitive Hematopoiesis in Zebrafish

2021 ◽  
Vol 9 ◽  
Author(s):  
Chong Zhang ◽  
Rui Huang ◽  
Xirui Ma ◽  
Jiehui Chen ◽  
Xinlu Han ◽  
...  
Keyword(s):  
Ribosome Biogenesis ◽  
Target Genes ◽  
P53 Protein ◽  
Ribosomal Subunit ◽  
Dependent Manner ◽  
Loss Of Function ◽  
Independent Manner ◽  
Hematopoietic Stem ◽  
Digestive Organs ◽  
Stem And Progenitor Cells

Ribosome biogenesis is a fundamental activity in cells. Ribosomal dysfunction underlies a category of diseases called ribosomopathies in humans. The symptomatic characteristics of ribosomopathies often include abnormalities in craniofacial skeletons, digestive organs, and hematopoiesis. Consistently, disruptions of ribosome biogenesis in animals are deleterious to embryonic development with hypoplasia of digestive organs and/or impaired hematopoiesis. In this study, ltv1, a gene involved in the small ribosomal subunit assembly, was knocked out in zebrafish by clustered regularly interspaced short palindromic repeats (CRISPRs)/CRISPR associated protein 9 (Cas9) technology. The recessive lethal mutation resulted in disrupted ribosome biogenesis, and ltv1Δ14/Δ14 embryos displayed hypoplastic craniofacial cartilage, digestive organs, and hematopoiesis. In addition, we showed that the impaired cell proliferation, instead of apoptosis, led to the defects in exocrine pancreas and hematopoietic stem and progenitor cells (HSPCs) in ltv1Δ14/Δ14 embryos. It was reported that loss of function of genes associated with ribosome biogenesis often caused phenotypes in a P53-dependent manner. In ltv1Δ14/Δ14 embryos, both P53 protein level and the expression of p53 target genes, Δ113p53 and p21, were upregulated. However, knockdown of p53 failed to rescue the phenotypes in ltv1Δ14/Δ14 larvae. Taken together, our data demonstrate that LTV1 ribosome biogenesis factor (Ltv1) plays an essential role in digestive organs and hematopoiesis development in zebrafish in a P53-independent manner.

scholarly journals Fanconi anemia A protein participates in nucleolar homeostasis maintenance and ribosome biogenesis

2021 ◽  
Vol 7 (1) ◽  
pp. eabb5414
Author(s):  
Anna Gueiderikh ◽  
Frédérique Maczkowiak-Chartois ◽  
Guillaume Rouvet ◽  
Sylvie Souquère-Besse ◽  
Sébastien Apcher ◽  
...  
Keyword(s):  
Dna Damage ◽  
Fanconi Anemia ◽  
Stress Responses ◽  
Ribosome Biogenesis ◽  
Bone Marrow Failure ◽  
Loss Of Function ◽  
Independent Manner ◽  
Ribosomal Subunits ◽  
Nucleolar Proteins ◽  
Nucleolar Stress

Fanconi anemia (FA), the most common inherited bone marrow failure and leukemia predisposition syndrome, is generally attributed to alterations in DNA damage responses due to the loss of function of the DNA repair and replication rescue activities of the FANC pathway. Here, we report that FANCA deficiency, whose inactivation has been identified in two-thirds of FA patients, is associated with nucleolar homeostasis loss, mislocalization of key nucleolar proteins, including nucleolin (NCL) and nucleophosmin 1 (NPM1), as well as alterations in ribosome biogenesis and protein synthesis. FANCA coimmunoprecipitates with NCL and NPM1 in a FANCcore complex–independent manner and, unique among the FANCcore complex proteins, associates with ribosomal subunits, influencing the stoichiometry of the translational machineries. In conclusion, we have identified unexpected nucleolar and translational consequences specifically associated with FANCA deficiency that appears to be involved in both DNA damage and nucleolar stress responses, challenging current hypothesis on FA physiopathology.

scholarly journals Wounding and insect feeding trigger two independent MAPK pathways with distinct regulation and kinetics

2019 ◽  
Author(s):  
Cécile Sözen ◽  
Sebastian T. Schenk ◽  
Marie Boudsocq ◽  
Camille Chardin ◽  
Marilia Almeida-Trapp ◽  
...  
Keyword(s):  
Insect Feeding ◽  
Independent Manner ◽  
Clade C ◽  
Short And Long Term ◽  
Abiotic And Biotic Factors ◽  
Parallel Activation ◽  
Rapid Signaling ◽  
Complex Signaling ◽  
Ja Signaling ◽  
Rapid Activation

AbstractWounding is caused by abiotic and biotic factors and triggers complex short- and long-term responses at the local and systemic level. These responses are under the control of complex signaling pathways, which are still poorly understood. Here, we show that the rapid activation of MKK4/5-MPK3/6 by wounding is independent of jasmonic acid (JA) signaling and that, contrary to what happens in tobacco, this fast module does not control wound-triggered JA accumulation in Arabidopsis. We also demonstrate that a second MAPK module, constituted by MKK3 and the clade-C MAPKs MPK1/2/7, is activated by wounding in an independent manner. We provide evidence that the activation of this MKK3-MPK1/2/7 module occurs mainly through wound-induced JA production via the transcriptional regulation of upstream clade-III MAP3Ks and particularly MAP3K14. We show that mkk3 mutant plants are more susceptible to the larvae of the generalist lepidopteran herbivore Spodoptera littoralis, indicating that the MKK3-MPK1/2/7 module is involved in counteracting insect feeding.One sentence summaryWounding induces the parallel activation of a rapid signaling module (MKK4/5-MPK3/6) and a JA-dependent slow one (MAP3K14-MKK3-MPK1/2/7/14) to restrict insect feeding.

scholarly journals Early life adversity promotes resilience to opioid addiction-related phenotypes in male rats and sex-specific transcriptional changes

2021 ◽  
Vol 118 (8) ◽  
pp. e2020173118
Author(s):  
Evelyn Ordoñes Sanchez ◽  
Charlotte C. Bavley ◽  
Andre U. Deutschmann ◽  
Rachel Carpenter ◽  
Drew R. Peterson ◽  
...  
Keyword(s):  
Early Life ◽  
Treatment Options ◽  
Progressive Ratio ◽  
Molecular Signature ◽  
Male Rats ◽  
Stress Inoculation ◽  
Early Life Adversity ◽  
Transcriptional Changes ◽  
Drug Naïve ◽  
Male Specific

Experiencing some early life adversity can have an “inoculating” effect that promotes resilience in adulthood. However, the mechanisms underlying stress inoculation are unknown, and animal models are lacking. Here we used the limited bedding and nesting (LBN) model of adversity to evaluate stress inoculation of addiction-related phenotypes. In LBN, pups from postnatal days 2 to 9 and their dams were exposed to a low-resource environment. In adulthood, they were tested for addiction-like phenotypes and compared to rats raised in standard housing conditions. High levels of impulsivity are associated with substance abuse, but in males, LBN reduced impulsive choice compared to controls. LBN males also self-administered less morphine and had a lower breakpoint on a progressive ratio reinforcement schedule than controls. These effects of LBN on addiction-related behaviors were not found in females. Because the nucleus accumbens (NAc) mediates these behaviors, we tested whether LBN altered NAc physiology in drug-naïve and morphine-exposed rats. LBN reduced the frequency of spontaneous excitatory postsynaptic currents in males, but a similar effect was not observed in females. Only in males did LBN prevent a morphine-induced increase in the AMPA/NMDA ratio. RNA sequencing was performed to delineate the molecular signature in the NAc associated with LBN-derived phenotypes. LBN produced sex-specific changes in transcription, including in genes related to glutamate transmission. Collectively, these studies reveal that LBN causes a male-specific stress inoculation effect against addiction-related phenotypes. Identifying factors that promote resilience to addiction may reveal novel treatment options for patients.

scholarly journals Mutation and Copy Number Alterations Analysis of KIF23 in Glioma

2021 ◽  
Vol 12 ◽  
Author(s):  
Zheng Zhao ◽  
Zheng Wang ◽  
Zhao-Shi Bao ◽  
Wei-Zhen Gao ◽  
Yuan-Da Zhang ◽  
...  
Keyword(s):  
Copy Number ◽  
Mitotic Cell ◽  
Vital Role ◽  
Missense Mutations ◽  
Copy Number Alterations ◽  
Coding Region ◽  
Whole Exome ◽  
Tnf Α ◽  
Genome Level ◽  
Pan Cancer

In glioma, kinesin family member 23 (KIF23) is up-regulated and plays a vital role in oncogenesis. However, the mechanism underlying KIF23 overexpression in malignant glioma remains to be elucidated. This study aims to find potential causes of KIF23 high expression at genome level. To clarify this issue, we obtained point mutation and copy number alterations (CNAs) of KIF23 in 319 gliomas using whole-exome sequencing. Only two glioma samples with missense mutations in KIF23 coding region were identified, while 7 patients were detected with amplification of KIF23. Additional analysis showed that KIF23 amplification was significantly associated with higher expression of KIF23. Gene ontology analysis indicated that higher copy number of KIF23 was associated TNF-α signaling pathway and mitotic cell circle checkpoint, which probably caused by subsequent upregulated expression of KIF23. Moreover, pan-cancer analysis showed that gaining of copy number was significantly associated with higher expression of KIF23, consolidating our findings in glioma. Thus, it was deduced that elevated KIF23 expression in glioma tended to be caused by DNA copy number amplification, instead of mutation.

scholarly journals Mammalian WDR12 is a novel member of the Pes1–Bop1 complex and is required for ribosome biogenesis and cell proliferation

2005 ◽  
Vol 170 (3) ◽  
pp. 367-378 ◽  
Author(s):  
Michael Hölzel ◽  
Michaela Rohrmoser ◽  
Martin Schlee ◽  
Thomas Grimm ◽  
Thomas Harasim ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Mammalian Cells ◽  
Ribosome Biogenesis ◽  
Target Genes ◽  
Dominant Negative ◽  
Stable Complex ◽  
Dominant Negative Mutant ◽  
Proliferating Cells ◽  
Independent Manner

Target genes of the protooncogene c-myc are implicated in cell cycle and growth control, yet the linkage of both is still unexplored. Here, we show that the products of the nucleolar target genes Pes1 and Bop1 form a stable complex with a novel member, WDR12 (PeBoW complex). Endogenous WDR12, a WD40 repeat protein, is crucial for processing of the 32S precursor ribosomal RNA (rRNA) and cell proliferation. Further, a conditionally expressed dominant-negative mutant of WDR12 also blocks rRNA processing and induces a reversible cell cycle arrest. Mutant WDR12 triggers accumulation of p53 in a p19ARF-independent manner in proliferating cells but not in quiescent cells. Interestingly, a potential homologous complex of Pes1–Bop1–WDR12 in yeast (Nop7p–Erb1p–Ytm1p) is involved in the control of ribosome biogenesis and S phase entry. In conclusion, the integrity of the PeBoW complex is required for ribosome biogenesis and cell proliferation in mammalian cells.

scholarly journals A ribosome assembly stress response regulates transcription to maintain proteome homeostasis

2019 ◽  
Author(s):  
Benjamin Albert ◽  
Isabelle C. Kos-Braun ◽  
Anthony Henras ◽  
Christophe Dez ◽  
Maria Paula Rueda ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Stress Response ◽  
Ribosomal Rna ◽  
Ribosome Biogenesis ◽  
Target Genes ◽  
Insoluble Fraction ◽  
Ribosome Assembly ◽  
Proteotoxic Stress ◽  
Rapid Activation ◽  
Stress Pathway

AbstractRibosome biogenesis is a complex and energy-demanding process requiring tight coordination of ribosomal RNA (rRNA) and ribosomal protein (RP) production. Alteration of any step in this process may impact growth by leading to proteotoxic stress. Although the transcription factor Hsf1 has emerged as a central regulator of proteostasis, how its activity is coordinated with ribosome biogenesis is unknown. Here we show that arrest of ribosome biogenesis in the budding yeast S. cerevisiae triggers rapid activation of a highly specific stress pathway that coordinately up-regulates Hsf1 target genes and down-regulates RP genes. Activation of Hsf1 target genes requires neo-synthesis of RPs, which accumulate in an insoluble fraction, leading to sequestration of the RP transcriptional activator Ifh1. Our data suggest that levels of newly-synthetized RPs, imported into the nucleus but not yet assembled into ribosomes, work to continuously balance Hsf1 and Ifh1 activity, thus guarding against proteotoxic stress during ribosome assembly.

scholarly journals Aging Regulates Post-Viral Asthmatic Airway Pathology

2021 ◽  
Author(s):  
Guy Hazan ◽  
Anna Eubanks ◽  
Carrie Gierasch ◽  
Jeffrey Atkinson ◽  
Carolyn Fox ◽  
...  
Keyword(s):  
Influenza A ◽  
Sendai Virus ◽  
Protective Effects ◽  
Independent Manner ◽  
Common Chronic Disease ◽  
Mhc Ii ◽  
Airway Pathology ◽  
Transcriptional Changes ◽  
High Level

Abstract Asthma is a common chronic disease of childhood, but for unknown reasons disease activity sometimes subsides as children mature. To understand why, we exposed mice across a range of ages to viral and allergic triggers of asthma exacerbations and airway pathology. We found that pathology induced by Sendai virus (SeV) or influenza A virus (IAV) occurred selectively in juvenile mice in a microbiome-independent manner, while the same phenotypes induced by allergens were insensitive to age. Age-specific responses to SeV included a juvenile bias towards type-2 airway inflammation that emerged early in infection and was lost with maturation. With aging, we observed progressive transcriptional changes to alveolar macrophages (AMs) including the acquisition of high-level MHC-II expression. Importantly, depleting AMs canceled the protective effects of maturity on post-viral airway pathology. Thus, aging of the lung-immune microenvironment influences chronic outcomes of respiratory viral infection and may help to explain childhood asthma remission.

scholarly journals RNA transcription modulates phase transition-driven nuclear body assembly

2015 ◽  
Vol 112 (38) ◽  
pp. E5237-E5245 ◽  
Author(s):  
Joel Berry ◽  
Stephanie C. Weber ◽  
Nilesh Vaidya ◽  
Mikko Haataja ◽  
Clifford P. Brangwynne
Keyword(s):  
Phase Transition ◽  
Phase Separation ◽  
Liquid Phase ◽  
Ribosome Biogenesis ◽  
Ostwald Ripening ◽  
Nuclear Body ◽  
Nuclear Bodies ◽  
Separation Mechanism ◽  
Independent Manner

Nuclear bodies are RNA and protein-rich, membraneless organelles that play important roles in gene regulation. The largest and most well-known nuclear body is the nucleolus, an organelle whose primary function in ribosome biogenesis makes it key for cell growth and size homeostasis. The nucleolus and other nuclear bodies behave like liquid-phase droplets and appear to condense from the nucleoplasm by concentration-dependent phase separation. However, nucleoli actively consume chemical energy, and it is unclear how such nonequilibrium activity might impact classical liquid–liquid phase separation. Here, we combine in vivo and in vitro experiments with theory and simulation to characterize the assembly and disassembly dynamics of nucleoli in early Caenorhabditis elegans embryos. In addition to classical nucleoli that assemble at the transcriptionally active nucleolar organizing regions, we observe dozens of “extranucleolar droplets” (ENDs) that condense in the nucleoplasm in a transcription-independent manner. We show that growth of nucleoli and ENDs is consistent with a first-order phase transition in which late-stage coarsening dynamics are mediated by Brownian coalescence and, to a lesser degree, Ostwald ripening. By manipulating C. elegans cell size, we change nucleolar component concentration and confirm several key model predictions. Our results show that rRNA transcription and other nonequilibrium biological activity can modulate the effective thermodynamic parameters governing nucleolar and END assembly, but do not appear to fundamentally alter the passive phase separation mechanism.

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