scholarly journals mRNA Editing, Processing and Quality Control in Caenorhabditis elegans

Genetics ◽  
2020 ◽  
Vol 215 (3) ◽  
pp. 531-568
Author(s):  
Joshua A. Arribere ◽  
Hidehito Kuroyanagi ◽  
Heather A. Hundley
Keyword(s):  
Quality Control ◽  
Caenorhabditis Elegans ◽  
Transcription Initiation ◽  
Control Mechanisms ◽  
Mrna Editing ◽  
Protein Coding ◽  
C Elegans ◽  
Expression Of Genes ◽  
Dynamic Expression ◽  
Specific Sequences

While DNA serves as the blueprint of life, the distinct functions of each cell are determined by the dynamic expression of genes from the static genome. The amount and specific sequences of RNAs expressed in a given cell involves a number of regulated processes including RNA synthesis (transcription), processing, splicing, modification, polyadenylation, stability, translation, and degradation. As errors during mRNA production can create gene products that are deleterious to the organism, quality control mechanisms exist to survey and remove errors in mRNA expression and processing. Here, we will provide an overview of mRNA processing and quality control mechanisms that occur in Caenorhabditis elegans, with a focus on those that occur on protein-coding genes after transcription initiation. In addition, we will describe the genetic and technical approaches that have allowed studies in C. elegans to reveal important mechanistic insight into these processes.

scholarly journals hecd-1 Modulates Notch Activity in Caenorhabditis elegans

2015 ◽  
Vol 5 (3) ◽  
pp. 353-359 ◽  
Author(s):  
Yunting Chen ◽  
Iva Greenwald
Keyword(s):  
Quality Control ◽  
Caenorhabditis Elegans ◽  
Cell Fate ◽  
Germ Line ◽  
Notch Pathway ◽  
Cell Fate Decisions ◽  
Notch Activity ◽  
C Elegans ◽  
Somatic Gonad ◽  
Constitutively Active

Abstract Notch is a receptor that mediates cell–cell interactions that specify binary cell fate decisions in development and tissue homeostasis. Inappropriate Notch signaling is associated with cancer, and mutations in Notch pathway components have been associated with developmental diseases and syndromes. In Caenorhabditis elegans, suppressors of phenotypes associated with constitutively active LIN-12/Notch have identified many conserved core components and direct or indirect modulators. Here, we molecularly identify sel(ar584), originally isolated as a suppressor of a constitutively active allele of lin-12. We show that sel(ar584) is an allele of hecd-1, the ortholog of human HECDT1, a ubiquitin ligase that has been implicated in several different mammalian developmental events. We studied interactions of hecd-1 with lin-12 in the somatic gonad and with the other C. elegans Notch gene, glp-1, in the germ line. We found that hecd-1 acts as a positive modulator of lin-12/Notch activity in a somatic gonad context—the original basis for its isolation—but acts autonomously as a negative modulator of glp-1/Notch activity in the germ line. As the yeast ortholog of HECD-1, Ufd4p, has been shown to function in quality control, and C. elegans  HECD-1 has been shown to affect mitochondrial maintenance, we propose that the different genetic interactions between hecd-1 and Notch genes we observed in different cell contexts may reflect differences in quality control regulatory mechanisms or in cellular metabolism.

scholarly journals Caenorhabditis elegans Extracts Stimulate IAA Biosynthesis in Arthrobacter pascens ZZ21 via the Indole-3-pyruvic Acid Pathway

2021 ◽  
Vol 9 (5) ◽  
pp. 970
Author(s):  
Mengsha Li ◽  
Teng Li ◽  
Ming Zhou ◽  
Mengdi Li ◽  
Yexin Zhao ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Pyruvic Acid ◽  
Tca Cycle ◽  
C Elegans ◽  
Expression Of Genes ◽  
Soil Ecosystems ◽  
Beneficial Bacterium ◽  
Acid Pathway ◽  
Reduced Nicotinamide Adenine Dinucleotide ◽  
Iaa Biosynthesis

Inter-organismal metabolites play important roles in regulating organism behavior and the communication between organisms. Nematodes, the most abundant animals on earth, are crucial participants in soil ecosystems through their interactions with microbes. For example, bacterial-feeding nematodes increase the activity of indole-3-acetic acid (IAA)-producing bacteria and the IAA content in soil. However, the way in which these nematodes interact with bacteria and affect IAA biosynthesis is not well understood. Here, using the model nematode Caenorhabditis elegans and the plant-beneficial bacterium Arthrobacter pascens ZZ21, we examined the effects of nematode excretions or extracts on bacterial IAA biosynthesis. To explore the underlying regulatory mechanism in more detail, we performed transcriptome sequencing and metabolomic analysis. Our findings suggest that C. elegans extracts promote IAA biosynthesis in A. pascens ZZ21 by increasing the expression of genes and the abundance of intermediates involved in the indole-3-pyruvic acid (IPyA) pathway. C. elegans extracts also significantly influenced biosynthetic and metabolic activity in A. pascens ZZ21. Treatment with C. elegans extracts promoted pyruvate metabolism, the citrate cycle (TCA) cycle and the production of some TCA-cycle-related amino acids and inhibited oxidative phosphorylation, which induced the accumulation of reduced nicotinamide adenine dinucleotide (NADH). We propose that the extracts altered the metabolism of A. pascens ZZ21 to help the bacteria resist stress caused by their predator. Our findings indicate that bacterial-feeding nematodes mediate the interaction between nematodes and bacteria via their extracts, providing insights into the ecological function of C. elegans in soil.

scholarly journals Organismal Protein Homeostasis Mechanisms

Genetics ◽  
2020 ◽  
Vol 215 (4) ◽  
pp. 889-901 ◽  
Author(s):  
Thorsten Hoppe ◽  
Ehud Cohen
Keyword(s):  
Quality Control ◽  
Protein Quality ◽  
Protein Homeostasis ◽  
Control Mechanisms ◽  
Dynamic Regulation ◽  
C Elegans ◽  
Selective Degradation ◽  
Proteotoxic Stress ◽  
Health And Disease ◽  
Folded Proteins

Sustaining a healthy proteome is a lifelong challenge for each individual cell of an organism. However, protein homeostasis or proteostasis is constantly jeopardized since damaged proteins accumulate under proteotoxic stress that originates from ever-changing metabolic, environmental, and pathological conditions. Proteostasis is achieved via a conserved network of quality control pathways that orchestrate the biogenesis of correctly folded proteins, prevent proteins from misfolding, and remove potentially harmful proteins by selective degradation. Nevertheless, the proteostasis network has a limited capacity and its collapse deteriorates cellular functionality and organismal viability, causing metabolic, oncological, or neurodegenerative disorders. While cell-autonomous quality control mechanisms have been described intensely, recent work on Caenorhabditis elegans has demonstrated the systemic coordination of proteostasis between distinct tissues of an organism. These findings indicate the existence of intricately balanced proteostasis networks important for integration and maintenance of the organismal proteome, opening a new door to define novel therapeutic targets for protein aggregation diseases. Here, we provide an overview of individual protein quality control pathways and the systemic coordination between central proteostatic nodes. We further provide insights into the dynamic regulation of cellular and organismal proteostasis mechanisms that integrate environmental and metabolic changes. The use of C. elegans as a model has pioneered our understanding of conserved quality control mechanisms important to safeguard the organismal proteome in health and disease.

scholarly journals Effects of sugars and lipids on the growth and development of Caenorhabditis elegans

2019 ◽  
Author(s):  
Xiong Wang ◽  
Lin Zhang ◽  
Lei Zhang ◽  
Wenli Wang ◽  
Sihan Wei ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Stearic Acid ◽  
Growth And Development ◽  
Reproductive Capacity ◽  
C Elegans ◽  
High Sugar ◽  
Expression Of Genes ◽  
High Lipid ◽  
High Stearic Acid ◽  
Excessive Intake

AbstractExcessive intake of carbohydrates and fats causes over-nutrition, leading to a variety of diseases and complications. Here, we characterized the effects of different types of sugar and lipids on the growth and development of Caenorhabditis elegans. We measured the lifespan, reproductive capacity, and length of nematodes after sugars and lipids treatment alone and co-treatment of sugars and lipids. Furthermore, by using transcriptome sequencing technology, we studied the mechanisms underlying the damaged caused by high-sucrose and high-stearic acid on C. elegans. The results showed that a certain concentration of sugar and lipid promoted the growth and development of nematodes. However, excessive sugars and lipids shortened the lifespan and length of nematodes and destroyed their reproductive capacity. Based on the results of the orthogonal test, we selected 400 mmol/L sucrose and 500 μg/mL stearic acid to model a high-sugar and high-lipid diet for C. elegans. High-sugar and high-lipid intake altered the expression of genes involved in biofilm synthesis, genes that catalyze the synthesis and degradation of endogenous substances, and genes involved in innate immunity, resulting in physiological damage.

scholarly journals p24 Proteins and Quality Control of LIN-12 and GLP-1 Trafficking in Caenorhabditis elegans

1999 ◽  
Vol 145 (6) ◽  
pp. 1165-1175 ◽  
Author(s):  
Chenhui Wen ◽  
Iva Greenwald
Keyword(s):  
Quality Control ◽  
Caenorhabditis Elegans ◽  
Control Mechanism ◽  
Genetic Interactions ◽  
C Elegans ◽  
Golgi Transport ◽  
Allele Specific ◽  
Regulation Of Transport ◽  
Quality Control Mechanism ◽  
P24 Proteins

Mutations in the Caenorhabditis elegans sel-9 gene elevate the activity of lin-12 and glp-1, which encode members of the LIN-12/NOTCH family of receptors. Sequence analysis indicates SEL-9 is one of several C. elegans p24 proteins. Allele-specific genetic interactions suggest that reducing sel-9 activity increases the activity of mutations altering the extracellular domains of LIN-12 or GLP-1. Reducing sel-9 activity restores the trafficking to the plasma membrane of a mutant GLP-1 protein that would otherwise accumulate within the cell. Our results suggest a role for SEL-9 and other p24 proteins in the negative regulation of transport of LIN-12 and GLP-1 to the cell surface, and favor a role for p24 proteins in a quality control mechanism for endoplasmic reticulum–Golgi transport.

scholarly journals Surveillance-ready transcription: nuclear RNA decay as a default fate

Open Biology ◽  
2018 ◽  
Vol 8 (3) ◽  
pp. 170270 ◽  
Author(s):  
Stefan Bresson ◽  
David Tollervey
Keyword(s):  
Quality Control ◽  
Rna Decay ◽  
Control Mechanisms ◽  
Protein Coding ◽  
Nuclear Rna ◽  
Rna Quality Control ◽  
Spurious Transcription ◽  
Rna Biogenesis ◽  
Bona Fide ◽  
Nascent Transcripts

Eukaryotic cells synthesize enormous quantities of RNA from diverse classes, most of which are subject to extensive processing. These processes are inherently error-prone, and cells have evolved robust quality control mechanisms to selectively remove aberrant transcripts. These surveillance pathways monitor all aspects of nuclear RNA biogenesis, and in addition remove nonfunctional transcripts arising from spurious transcription and a host of non-protein-coding RNAs (ncRNAs). Surprisingly, this is largely accomplished with only a handful of RNA decay enzymes. It has, therefore, been unclear how these factors efficiently distinguish between functional RNAs and huge numbers of diverse transcripts that must be degraded. Here we describe how bona fide transcripts are specifically protected, particularly by 5′ and 3′ modifications. Conversely, a plethora of factors associated with the nascent transcripts all act to recruit the RNA quality control, surveillance and degradation machinery. We conclude that initiating RNAPII is ‘surveillance ready’, with degradation being a default fate for all transcripts that lack specific protective features. We further postulate that this promiscuity is a key feature that allowed the proliferation of vast numbers of ncRNAs in eukaryotes, including humans.

scholarly journals The FOXO’s Advantages of Being a Family: Considerations on Function and Evolution

Cells ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 787 ◽  
Author(s):  
Michel Schmitt-Ney
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
Caenorhabditis Elegans ◽  
Akt Pathway ◽  
Dna Binding Domain ◽  
Cell Type ◽  
Nematode Caenorhabditis Elegans ◽  
Protein Coding ◽  
C Elegans ◽  
Foxo Transcription Factors

The nematode Caenorhabditis elegans possesses a unique (with various isoforms) FOXO transcription factor DAF-16, which is notorious for its role in aging and its regulation by the insulin-PI3K-AKT pathway. In humans, five genes (including a protein-coding pseudogene) encode for FOXO transcription factors that are targeted by the PI3K-AKT axis, such as in C. elegans. This common regulation and highly conserved DNA-binding domain are the pillars of this family. In this review, I will discuss the possible meaning of possessing a group of very similar proteins and how it can generate additional functionality to more complex organisms. I frame this discussion in relation to the much larger super family of Forkhead proteins to which they belong. FOXO members are very often co-expressed in the same cell type. The overlap of function and expression creates a certain redundancy that might be a safeguard against the accidental loss of FOXO function, which could otherwise lead to disease, particularly, cancer. This is one of the points that will be examined in this “family affair” report.

scholarly journals Role of insulin/insulin-like growth factor-1 signaling pathway genes on the lifespan of Caenorhabditis elegans

2020 ◽  
Vol 11 (2) ◽  
Author(s):  
Siti Bazilah Zulkefli ◽  
Ahmad Nazrun Shuid ◽  
Goon Jo Aan
Keyword(s):  
Caenorhabditis Elegans ◽  
Growth Factor ◽  
Signaling Pathway ◽  
Model Organism ◽  
Insulin Like Growth Factor ◽  
C Elegans ◽  
Expression Of Genes ◽  
Differential Expression Of Genes

Aging process is influenced by the insulin/insulin-like growth factor-1 signaling (IIS) pathway or IGF-1 signaling pathway. Studies done on the genes of this pathway were found to affect longevity. However, no conclusive results have been drawn.The purpose of this systematic review is to summarize the function of genes involved in the IIS pathway of Caenorhabditis Elegans (C. elegans), a nematode commonly used as a model organism in molecular genetics and developmental biology. A literature search for relevant studies was done through PubMed and Scopus databases using MeSH keywords Caenorhabditis elegans, C. elegans, nematode, genes, RNA, DNA, IIS pathway, IGF pathway, lifespan, and longevity. The search was limited to studies that were published in the last ten years (2008-May 2018). After exclusion of duplicates, review papers, human, in vitro, and other organismal studies, a total of 76 research articles were selected for further assessments. Data relevant to the effects of IIS genes on the lifespan ofC. eleganswas independently extracted. Reduction of daf-2 and age-1 and overexpression of sir-2.1 were reported to promote increment of the lifespan of C. elegans.  Furthermore, differentially expressed genes that were involved in the protection against oxidative stress, pathogen attack, and toxicity includeins-18, numr-1/-2, sgk-1, and rgs-1. The knockdown of daf-2, age-1, and overexpression of sir-2.1 genes prolonged the lifespan of C. elegans while knockdown of daf-16, hsf-1, sir-2.1 as well as skn-1 shorten the lifespan of C. elegans.In conclusion, the differential expression of genes in the IIS pathway prolongs the lifespan of C. elegans.

A Caenorhabditis elegans model of Yersinia infection: biofilm formation on a biotic surface

Microbiology ◽  
2003 ◽  
Vol 149 (11) ◽  
pp. 3221-3229 ◽  
Author(s):  
G. W. P. Joshua ◽  
A. V. Karlyshev ◽  
M. P. Smith ◽  
K. E. Isherwood ◽  
R. W. Titball ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Biofilm Formation ◽  
Yersinia Pseudotuberculosis ◽  
Model Organism ◽  
Severe Infection ◽  
Evolutionary Divergence ◽  
Control Mechanisms ◽  
C Elegans ◽  
Pathway Gene ◽  
Genes Encoding

To investigate Yersinia pathogenicity and the evolutionary divergence of the genus, the effect of pathogenic yersiniae on the model organism Caenorhabditis elegans was studied. Three strains of Yersinia pestis, including a strain lacking pMT1, caused blockage and death of C. elegans; one strain, lacking the haemin storage (hms) locus, caused no effect. Similarly, 15 strains of Yersinia enterocolitica caused no effect. Strains of Yersinia pseudotuberculosis showed different levels of pathogenicity. The majority of strains (76 %) caused no discernible effect; 5 % caused a weak infection, 9·5 % an intermediate infection, and 9·5 % a severe infection. There was no consistent relationship between serotype and severity of infection; nor was there any relationship between strains causing infection of C. elegans and those able to form a biofilm on an abiotic surface. Electron microscope and cytochemical examination of infected worms indicated that the infection phenotype is a result of biofilm formation on the head of the worm. Seven transposon mutants of Y. pseudotuberculosis strain YPIII pIB1 were completely or partially attenuated; mutated genes included genes encoding proteins involved in haemin storage and lipopolysaccharide biosynthesis. A screen of 15 defined C. elegans mutants identified four where mutation caused (complete) resistance to infection by Y. pseudotuberculosis YPIII pIB1. These mutants, srf-2, srf-3, srf-5 and the dauer pathway gene daf-1, also exhibit altered binding of lectins to the nematode surface. This suggests that biofilm formation on a biotic surface is an interactive process involving both bacterial and invertebrate control mechanisms.

scholarly journals Nonselective autophagy reduces mitochondrial content during starvation in Caenorhabditis elegans

2018 ◽  
Vol 315 (6) ◽  
pp. C781-C792 ◽  
Author(s):  
Jonathan D. Hibshman ◽  
Tess C. Leuthner ◽  
Chelsea Shoben ◽  
Danielle F. Mello ◽  
David R. Sherwood ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Mitochondrial Function ◽  
Mitochondrial Fission ◽  
Control Mechanisms ◽  
Mtdna Copy Number ◽  
Mitochondrial Content ◽  
C Elegans ◽  
Larval Stages ◽  
Developmental Arrest ◽  
Cellular Energetics

Starvation significantly alters cellular physiology, and signs of aging have been reported to occur during starvation. Mitochondria are essential to the regulation of cellular energetics and aging. We sought to determine whether mitochondria exhibit signs of aging during starvation and whether quality control mechanisms regulate mitochondrial physiology during starvation. We describe effects of starvation on mitochondria in the first and third larval stages of the nematode Caenorhabditis elegans. When starved, C. elegans larvae enter developmental arrest. We observed fragmentation of the mitochondrial network, a reduction in mitochondrial DNA (mtDNA) copy number, and accumulation of DNA damage during starvation-induced developmental arrest. Mitochondrial function was also compromised by starvation. Starved worms had lower basal, maximal, and ATP-linked respiration. These observations are consistent with reduced mitochondrial quality, similar to mitochondrial phenotypes during aging. Using pharmacological and genetic approaches, we found that worms deficient for autophagy were short-lived during starvation and recovered poorly from extended starvation, indicating sensitivity to nutrient stress. Autophagy mutants unc-51/Atg1 and atg-18/Atg18 maintained greater mtDNA content than wild-type worms during starvation, suggesting that autophagy promotes mitochondrial degradation during starvation. unc-51 mutants also had a proportionally smaller reduction in oxygen consumption rate during starvation, suggesting that autophagy also contributes to reduced mitochondrial function. Surprisingly, mutations in genes involved in mitochondrial fission and fusion as well as selective mitophagy of damaged mitochondria did not affect mitochondrial content during starvation. Our results demonstrate the profound influence of starvation on mitochondrial physiology with organismal consequences, and they show that these physiological effects are influenced by autophagy.

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