scholarly journals N6-adenosine methylation of ribosomal RNA affects lipid oxidation and stress resistance

2020 ◽  
Vol 6 (17) ◽  
pp. eaaz4370 ◽  
Author(s):  
Noa Liberman ◽  
Zach K. O’Brown ◽  
Andrew Scott Earl ◽  
Konstantinos Boulias ◽  
Maxim V. Gerashchenko ◽  
...  

During stress, global translation is reduced, but specific transcripts are actively translated. How stress-responsive mRNAs are selectively translated is unknown. We show that METL-5 methylates adenosine 1717 on 18S ribosomal RNA in C. elegans, enhancing selective ribosomal binding and translation of specific mRNAs. One of these mRNAs, CYP-29A3, oxidizes the omega-3 polyunsaturated fatty acid eicosapentaenoic acid to eicosanoids, key stress signaling molecules. While metl-5–deficient animals grow normally under homeostatic conditions, they are resistant to a variety of stresses. metl-5 mutant worms also show reduced bioactive lipid eicosanoids and dietary supplementation of eicosanoid products of CYP-29A3 restores stress sensitivity of metl-5 mutant worms. Thus, methylation of a specific residue of 18S rRNA by METL-5 selectively enhances translation of cyp-29A3 to increase production of eicosanoids, and blocking this pathway increases stress resistance. This study suggests that ribosome methylation can facilitate selective translation, providing another layer of regulation of the stress response.

2021 ◽  
Author(s):  
Noa Liberman ◽  
Maxim V. Gerashchenko ◽  
Konstantinos Boulias ◽  
Fiona G MacWhinnie ◽  
Albert Kejun Ying ◽  
...  

SummaryHeritable non-genetic information can regulate a variety of complex phenotypes. However, what specific non-genetic cues are transmitted from parents to their descendants are poorly understood. Here, we perform metabolic methyl-labelling experiments to track the heritable transmission of methylation from ancestors to their descendants in the nematode Caenorhabditis elegans. We find that methylation is transmitted to descendants in proteins, RNA, DNA and lipids. We further find that in response to parental starvation, fed naïve progeny display reduced fertility, increased heat stress resistance, and extended longevity. This intergenerational hormesis is accompanied by a heritable increase in N6’-dimethyl adenosine (m6,2A) on the 18S ribosomal RNA at adenosines 1735 and 1736. We identified the conserved DIMT-1 as the m6,2A methyltransferase in C. elegans and find that dimt-1 is required for the intergenerational hormesis phenotypes. This study provides the first labeling and tracking of heritable non-genetic material across generations and demonstrates the importance of rRNA methylation for regulating the heritable response to starvation.


Science ◽  
2011 ◽  
Vol 335 (6064) ◽  
pp. 82-85 ◽  
Author(s):  
M. Olivia Casanueva ◽  
Alejandro Burga ◽  
Ben Lehner

Mutations often have consequences that vary across individuals. Here, we show that the stimulation of a stress response can reduce mutation penetrance in Caenorhabditis elegans. Moreover, this induced mutation buffering varies across isogenic individuals because of interindividual differences in stress signaling. This variation has important consequences in wild-type animals, producing some individuals with higher stress resistance but lower reproductive fitness and other individuals with lower stress resistance and higher reproductive fitness. This may be beneficial in an unpredictable environment, acting as a “bet-hedging” strategy to diversify risk. These results illustrate how transient environmental stimuli can induce protection against mutations, how environmental responses can underlie variable mutation buffering, and how a fitness trade-off may make variation in stress signaling advantageous.


2020 ◽  
Vol 98 (Supplement_3) ◽  
pp. 196-197
Author(s):  
Woo Jung Seok ◽  
Je min Ahn ◽  
Jing Hu ◽  
Dexin Dang ◽  
Yanjiao Li ◽  
...  

Abstract The objective of this study was to evaluate the effects of dietary supplementation of coated omega-3 fatty acid (n-3 CFA) by corn cob power silica on performance of weaning pigs. A total of 200 weaned pigs [(Landrace x Yorkshire) x Duroc, average initial body weight at 6.97 ± 1.22 kg] were randomly assigned to four experimental treatments in a 6-week experiment in 3 phases as follows: CON, basal diet; 2) 0.3CFA, CON + phase 1(0.3% n-3CFA), phase 2(0.2% n-3CFA), phase 3(0.1% n-3CFA); 3) 0.6CFA, CON + phase 1(0.6% n-3CFA), phase 2(0.4% n-3CFA), phase 3(0.2% n-3CFA); 4) 0.9CFA, CON + phase 1(0.9% n-3CFA), phase 2(0.6% n-3CFA), phase 3 (0.3% n-3CFA). Each treatment had 10 replicates with 5 pigs (three gilts and two barrows) per replicate. The data were analyzed using the GLM procedure of SAS as a randomized complete block design. Pen served as the experimental unit. Linear, quadratic and cubic polynomial contrasts were used to examine effect of dietary treatment with coated n-3FA in the basal diet. Variability in the data was expressed as the standard error of means and P< 0.05 was considered to statistically significant. Increasing the level of n-3CFA in the diet linearly increased ADG and G/F of pigs (Table 1). Increasing the level of n-3CFA showed a linear increment in the digestibility of DM (83.59, 84.38, 85.13, 85.89 %) whereas nitrogen digestibility (81.79, 82.38, 82.96, 83.64 %) showed a trend (linear effect, p=0.0594) at the end of experiment. The fecal lactobacillus count was increased (7.22, 7.27, 7.33, 7.35 log10cfu/g) with the increase in the supplemental level of n-3CFA (linear effect; p< 0.05). However, there were no differences in the concentration of serum haptoglobin, or fecal E. coli, Clostridium and Salmonella counts despite the increase in n-3CFA levels in the diet. Supplementation of the diet with coated n-3 fatty acids positively affected growth performance and digestibility of dry matter and nitrogen, and enhanced the count of lactobacillus in weaning pigs.


2021 ◽  
pp. 1-17
Author(s):  
Mani Iyer Prasanth ◽  
James Michael Brimson ◽  
Dicson Sheeja Malar ◽  
Anchalee Prasansuklab ◽  
Tewin Tencomnao

BACKGROUND: Streblus asper Lour., has been reported to have anti-aging and neuroprotective efficacies in vitro. OBJECTIVE: To analyze the anti-aging, anti-photoaging and neuroprotective efficacies of S. asper in Caenorhabditis elegans. METHODS: C. elegans (wild type and gene specific mutants) were treated with S. asper extract and analyzed for lifespan and other health benefits through physiological assays, fluorescence microscopy, qPCR and Western blot. RESULTS: The plant extract was found to increase the lifespan, reduce the accumulation of lipofuscin and modulate the expression of candidate genes. It could extend the lifespan of both daf-16 and daf-2 mutants whereas the pmk-1 mutant showed no effect. The activation of skn-1 was observed in skn-1::GFP transgenic strain and in qPCR expression. Further, the extract can extend the lifespan of UV-A exposed nematodes along with reducing ROS levels. Additionally, the extract also extends lifespan and reduces paralysis in Aβ transgenic strain, apart from reducing Aβ expression. CONCLUSIONS: S. asper was able to extend the lifespan and healthspan of C. elegans which was independent of DAF-16 pathway but dependent on SKN-1 and MAPK which could play a vital role in eliciting the anti-aging, anti-photoaging and neuroprotective effects, as the extract could impart oxidative stress resistance and neuroprotection.


Nutrients ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 213
Author(s):  
Lauren A. Roach ◽  
Mitchell K. Byrne ◽  
Steven J. Howard ◽  
Stuart J. Johnstone ◽  
Marijka Batterham ◽  
...  

Self-regulation, the regulation of behaviour in early childhood, impacts children’s success at school and is a predictor of health, wealth, and criminal outcomes in adulthood. Self-regulation may be optimised by dietary supplementation of omega-3 long-chain polyunsaturated fatty acids (n-3 LCPUFAs). The aim of the “Omega Kid” study is to investigate the feasibility of a protocol to investigate whether n-3 LCPUFA supplementation enhances self-regulation in preschool-aged children. The protocol assessed involved a double-blind, randomised, placebo-controlled trial of 12 weeks duration, with an intervention of 1.6 g of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) per day (0.3 g EPA and 1.3 g DHA) in a microencapsulated powder compared to placebo. Children (n = 78; 40 boys and 38 girls) aged 3–5 years old were recruited and randomly allocated to the treatment (n = 39) or placebo group (n = 39). The HS–Omega-3 Index® served as a manipulation check on the delivery of either active (n-3 LCPUFAs) or placebo powders. Fifty-eight children (76%) completed the intervention (28–30 per group). Compliance to the study protocol was high, with 92% of children providing a finger-prick blood sample at baseline and high reported-adherence to the study intervention (88%). Results indicate that the protocol is feasible and may be employed in an adequately powered clinical trial to test the hypothesis that n-3 LCPUFA supplementation will improve the self-regulation of preschool-aged children.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hye-Jin Kim ◽  
Dongwook Kim ◽  
Kwan-Woo Kim ◽  
Sang-Hoon Lee ◽  
Aera Jang

AbstractWe used 16S ribosomal RNA sequencing to evaluate changes in the gut microbiota of mice fed a diet supplemented with either raw or cooked beef loin powder for 9 weeks. Male BALB/c mice (n = 60) were randomly allocated to five groups: mice fed AIN-93G chow (CON), chow containing 5% (5RB) and 10% (10RB) raw beef loin powder, and chow containing 5% (5CB) and 10% (10CB) cooked beef loin powder. Dietary supplementation with both RB and CB increased the relative abundance of Clostridiales compared to the CON diet (p < 0.05). Mice fed 10RB showed a significantly higher relative abundance of Firmicutes (p = 0.018) and Lactobacillus (p = 0.001) than CON mice, and the ratio of Firmicutes/Bacteroidetes showed an increasing trend in the 10RB mice (p > 0.05). Mice fed 10CB showed a higher abundance of Peptostreptococcaceae and a lower abundance of Desulfovibrionaceae compared with the CON mice (p < 0.05). Genes for glycan biosynthesis, which result in short-chain fatty acid synthesis, were enriched in the CB mice compared to the RB mice, which was correlated to a high abundance of Bacteroides. Overall, dietary RB and CB changed the gut microbiota of mice (p < 0.05).


1989 ◽  
Vol 36 (4) ◽  
pp. 653-660 ◽  
Author(s):  
William F. Clark ◽  
Anwar Parbtani ◽  
Murray W. Huff ◽  
Bruce Reid ◽  
Bruce J. Holub ◽  
...  

2005 ◽  
Vol 288 (2) ◽  
pp. C467-C474 ◽  
Author(s):  
S. Todd Lamitina ◽  
Kevin Strange

All cells adapt to hypertonic stress by regulating their volume after shrinkage, by accumulating organic osmolytes, and by activating mechanisms that protect against and repair hypertonicity-induced damage. In mammals and nematodes, inhibition of signaling from the DAF-2/IGF-1 insulin receptor activates the DAF-16/FOXO transcription factor, resulting in increased life span and resistance to some types of stress. We tested the hypothesis that inhibition of insulin signaling in Caenorhabditis elegans also increases hypertonic stress resistance. Genetic inhibition of DAF-2 or its downstream target, the AGE-1 phosphatidylinositol 3-kinase, confers striking resistance to a normally lethal hypertonic shock in a DAF-16-dependent manner. However, insulin signaling is not inhibited by or required for adaptation to hypertonic conditions. Microarray studies have identified 263 genes that are transcriptionally upregulated by DAF-16 activation. We identified 14 DAF-16-upregulated genes by RNA interference screening that are required for age- 1 hypertonic stress resistance. These genes encode heat shock proteins, proteins of unknown function, and trehalose synthesis enzymes. Trehalose levels were elevated approximately twofold in age- 1 mutants, but this increase was insufficient to prevent rapid hypertonic shrinkage. However, age- 1 animals unable to synthesize trehalose survive poorly under hypertonic conditions. We conclude that increased expression of proteins that protect eukaryotic cells against environmental stress and/or repair stress-induced molecular damage confers hypertonic stress resistance in C. elegans daf- 2/ age- 1 mutants. Elevated levels of solutes such as trehalose may also function in a cytoprotective manner. Our studies provide novel insights into stress resistance in animal cells and a foundation for new studies aimed at defining molecular mechanisms underlying these essential processes.


2016 ◽  
Vol 16 (4) ◽  
pp. 1045-1058 ◽  
Author(s):  
Essa Dirandeh ◽  
Armin Towhidi ◽  
Zarbakht Ansari ◽  
Saeeid Zeinoaldini ◽  
Mehdi Ganjkhanlou

Abstract The objective of this study was to investigate whether dietary supplementation with different polyunsaturated fatty acids (PUFA s) affects expression of genes related to somatotropic axis and the plasma concentrations of insulin, glucose, non-esterified fatty acids (NEFA), beta hydroxyl butyrate acids (BHBA) and insulin-like growth factor 1 (IGF1) and milk fatty acids profile. Right after calving, Holstein cows (n=45) were randomly assigned to one of three diets supplemented with roasted whole soybean as a source of omega-6 PUFA (omega-6, n=15), linseed as a source of omega-3 PUFA (omega-3, n=15) or palm oil (control, n=15). Each cow was in the study over a period of 70 days. Blood samples were collected every two weeks from day 1 to 70 of lactation and plasma concentrations of insulin, glucose, NEFA, BHBA and IGF1 were determined. Liver samples were taken from a subset of 18 cows (6 per diet) at day 70 postpartum and hepatic mRNA level of total growth hormone-receptor 1A (GHR1A), insulin receptor (INSR), IGF1 and insulinlike growth factor binding protein (IGFBP2) was assessed. Experimental diets did not affect milk yield. Plasma glucose and insulin concentrations were greater for omega-3 treatment compared to omega-6 and control treatments. Cows fed diets enriched in omega-3 exhibited greater INSR and GHR1A mRNA expression, and a tendency for greater IGF1 mRNA expression in the liver compared to omega-6 and control cows. Plasma IGF1 concentration was significantly higher in omega-3 treatment compared with omega-6 and control treatments. Results of this study suggest that feeding omega-3 PUFA s during early postpartum couples with the somatotropic axis, leading to an increase in plasma IGF1 concentration in dairy cows.


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