Immune response to pathogens is energetically expensive to the host; however, the cellular source of energy to fuel immune response remains unknown. In this study, we show that Caenorhabditis elegans exposed to pathogenic Gram-positive and Gram-negative bacteria or yeast rapidly utilizes lipid droplets, the major energy reserve. The nematode’s response to the pathogenic bacterium Enterococcus faecalis entails metabolic rewiring for the upregulation of several genes involved in lipid utilization and downregulation of lipid synthesis genes. Genes encoding acyl-CoA synthetase ACS-2, involved in lipid metabolism, and flavin monooxygenase FMO-2, involved in detoxification, are two highly upregulated genes during E. faecalis infection. We find that both ACS-2 and FMO-2 are necessary for survival and rely on NHR-49, a peroxisome proliferator-activated receptor alpha (PPARα) ortholog, for upregulation during E. faecalis infection. Thus, NHR-49 regulates an immunometabolic axis of survival in C. elegans by modulating breakdown of lipids as well as immune effector production upon E. faecalis exposure.
The G protein‐coupled receptor (GPCR) encoding family of genes constitutes more than 6% of genes in Caenorhabditis elegans genome. GPCRs control behavior, innate immunity, chemotaxis, and food search behavior. Here, we show that C. elegans longevity is regulated by a chemosensory GPCR STR‐2, expressed in AWC and ASI amphid sensory neurons. STR‐2 function is required at temperatures of 20°C and higher on standard Escherichia coli OP50 diet. Under these conditions, this neuronal receptor also controls health span parameters and lipid droplet (LD) homeostasis in the intestine. We show that STR‐2 regulates expression of delta‐9 desaturases, fat‐5, fat‐6 and fat‐7, and of diacylglycerol acyltransferase dgat‐2. Rescue of the STR‐2 function in either AWC and ASI, or ASI sensory neurons alone, restores expression of fat‐5, dgat‐2 and restores LD stores and longevity. Rescue of stored fat levels of GPCR mutant animals to wild‐type levels, with low concentration of glucose, rescues its lifespan phenotype. In all, we show that neuronal STR‐2 GPCR facilitates control of neutral lipid levels and longevity in C. elegans.
Untranslated regions of eukaryotic genes contain elements that in combination with proteins/RNAs modulate translation of individual messenger RNAs. Elements present in 5Ј-UTRs that influence translational efficiency include AUG sequence context, and presence of uAUGs/uORFs. To assess the level of 5Ј-UTR mediated translational regulation in rice, a genome-wide computational analysis of rice 5Ј-UTRs was carried out in comparison with 5Ј-UTRs of Arabidopsis. Rice 5Ј-UTRs were generally longer and more GC-rich than those of Arabidopsis. 30% of rice and 34% of Arabidopsis cDNAs contained upstream AUG triplets (uAUGs). For both organisms, a higher proportion of uAUG-less cDNAs possessed start codons which conformed to the consensus sequence context compared to uAUG-containing cDNAs. Although the GC composition of the start codon context varied between and within rice and Arabidopsis, the critical positions, ϩ4 and Ϫ3, were conserved. 24% of rice and 30% of Arabidopsis cDNAs possessed upstream open reading frames (uORFs). Combinatorial analyses of start-codon context, uAUG context and context of uAUGs of upstream open reading frames of individual genes indicate that about 30-34% of genes in rice and Arabidopsis are likely to be influenced at translational level by signals present in 5Ј-UTR as they possess uAUG/uORFs with sequence context conforming to the consensus sequence There was very little conservation of uAUG positions or uORFs between rice and Arabidopsis. However, there was conservation of uAUG positions between rice, wheat and barley.
Immune responses to pathogenic microbes include activation of resistance and tolerance mechanisms in the host both of which are energetically expensive. In this study, we show that C. elegans exposed to Gram positive bacteria Enterococcus faecalis and Staphylococcus aureus, rapidly utilizes lipid droplets, the major energy reserve in the nematode. Feeding on E. faecalis causes developmental arrest in C. elegans larvae and growth arrest in adults, pointing to starvation response. We find that nematode's early response to infection entails upregulation of 25 genes involved in lipid hydrolysis and downregulation of 13 lipid synthesis genes as early as 8 hours following exposure. We also show that lipid droplets play a protective role in C. elegans during infection. NHR-49, a PPARα ortholog, is required for E. faecalis induced betaoxidation of fatty acids and immune effector production. It regulates an immunometabolic axis required for survival of the nematode on E. faecalis. Our findings reveal a facet of nutritional immunity wherein lipid droplet homeostasis plays a central role in nematode microbe interactions.
Genome-wide computational analysis for small nuclear RNA (snRNA) genes resulted in identification of 76 and 73 putative snRNA genes from indica and japonica rice genomes, respectively. We used the basic criteria of a minimum of 70 % sequence identity to the plant snRNA gene used for genome search, presence of conserved promoter elements: TATA box, USE motif and monocot promoter specific elements (MSPs) and extensive sequence alignment to rice / plant expressed sequence tags to denote predicted sequence as snRNA genes. Comparative sequence analysis with snRNA genes from other organisms and predicted secondary structures showed that there is overall conservation of snRNA sequence and structure with plant specific features (presence of TATA box in both polymerase II and III transcribed genes, location of USE motif upstream to the TATA box at fixed but different distance in polymerase II and polymerase III transcribed snRNA genes) and the presence of multiple monocot specific MSPs upstream to the USE motif. Detailed analysis results including all multiple sequence alignments, sequence logos, secondary structures, sequences etc are available at http://kulab.org
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