Dietary restriction induces posttranscriptional regulation of longevity genes

Rollins, Jarod; Shaffer, Dan; Snow, Santina; Kapahi, Pankaj; Rogers, Aric N.

doi:10.26508/lsa.201800281

Cited by 33 publications

(17 citation statements)

References 135 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…GO-term enrichment using DAVID (version 6.7) was performed as previously described ( Rollins et al, 2019 ). Only protein-coding genes with detectable expression (base mean >1), a fold-change of >2 and an adjusted p-value of <0.10 were considered.…”

Section: Methodsmentioning

confidence: 99%

The ribosomal RNA m5C methyltransferase NSUN-1 modulates healthspan and oogenesis in Caenorhabditis elegans

Heissenberger

Rollins

Krammer

et al. 2020

eLife

Self Cite

View full text Add to dashboard Cite

Our knowledge about the repertoire of ribosomal RNA modifications and the enzymes responsible for installing them is constantly expanding. Previously, we reported that NSUN-5 is responsible for depositing m5C at position C2381 on the 26S rRNA in Caenorhabditis elegans. Here, we show that NSUN-1 is writing the second known 26S rRNA m5C at position C2982. Depletion of nsun-1 or nsun-5 improved thermotolerance and slightly increased locomotion at midlife, however, only soma-specific knockdown of nsun-1 extended lifespan. Moreover, soma-specific knockdown of nsun-1 reduced body size and impaired fecundity, suggesting non-cell-autonomous effects. While ribosome biogenesis and global protein synthesis were unaffected by nsun-1 depletion, translation of specific mRNAs was remodeled leading to reduced production of collagens, loss of structural integrity of the cuticle, and impaired barrier function. We conclude that loss of a single enzyme required for rRNA methylation has profound and highly specific effects on organismal development and physiology.

show abstract

Section: Methodsmentioning

confidence: 99%

The ribosomal RNA m5C methyltransferase NSUN-1 modulates healthspan and oogenesis in Caenorhabditis elegans

Heissenberger

Rollins

Krammer

et al. 2020

eLife

Self Cite

View full text Add to dashboard Cite

show abstract

“…Full results are contained in the supplements. UTR characterization and RBP motif enrichment were performed as previously described (Rollins et al, 2019) using only protein-coding genes with detectable expression (base mean > 1), a fold change of > 2 and an adjusted p-value of < 0.10.…”

Section: Methodsmentioning

confidence: 99%

The ribosomal RNA m⁵C methyltransferase NSUN-1 modulates healthspan and oogenesis in Caenorhabditis elegans

Heissenberger

Krammer

Rollins

et al. 2020

Preprint

View full text Add to dashboard Cite

21Our knowledge about the repertoire of ribosomal RNA modifications and the enzymes 22 responsible for installing them is constantly expanding. Previously, we reported that NSUN-5 23 is responsible for depositing m 5 C at position C2381 on the 26S rRNA in Caenorhabditis 24 elegans. 25 Here, we show that NSUN-1 is writing the second known 26S rRNA m 5 C at position C2982. 26 Depletion of nsun-1 or nsun-5 improved locomotion at midlife and resistance against heat 27 stress, however, only soma-specific knockdown of nsun-1 extended lifespan. Moreover, 28 soma-specific knockdown of nsun-1 reduced body size and impaired fecundity, suggesting 29 non-cell-autonomous effects. While ribosome biogenesis and global protein synthesis were 30 unaffected by nsun-1 depletion, translation of specific mRNAs was remodelled leading to 31 reduced production of collagens, loss of structural integrity of the cuticle and impaired barrier 32 function. 33 We conclude that loss of a single enzyme required for rRNA methylation has profound and 34 highly specific effects on organismal physiology. 102Therefore, we investigated the RNA substrate of NSUN-1 (also formerly known as NOL-1, 103 NOL-2 or W07E6.1) and its potential roles in worm physiology. NSUN-1 is also a member 104 of the NOP2/Sun RNA methyltransferase family. Since there are only two known m 5 C 105 residues on worm 26S rRNA (Sharma and Lafontaine, 2015; Trixl and Lusser, 2019), one of 106 them at C2381, being installed by NSUN-5, we speculated that NSUN-1 might be required 107 6 for introducing the second m 5 C residue at position C2982. Notably, both 26S m 5 C sites are 108 localized close to important functional regions of the ribosome, and they are highly conserved 109 during evolution ( Fig. 1A,B). 110In order to test if NSUN-1 is involved in large ribosomal subunit m 5 C methylation, 26S 111 rRNA was purified from worms treated with siRNAs specific to NSUN-1-encoding mRNAs 112 on sucrose gradients, digested to single nucleosides and analysed by quantitative HPLC. In 113 our HPLC assay, the m 5 C nucleoside eluted at 12 min, as established with a m 5 C calibration 114 control (data not shown). 115The depletion of NSUN-1 was conducted in two genetic backgrounds: N2 (wildtype), and 116 NL2099 (an RNAi-hypersensitive strain due to mutation in rrf-3) (Figure 1-figure 117 supplement 1). Treating N2 worms with an empty control vector, not expressing any RNAi, 118did not significantly reduce the levels of 26S rRNA m 5 C methylation (Fig. 1C, 97% instead 119 of 100%). Interestingly, treating N2 worms with an RNAi construct targeting nsun-1 led to a 120 reduction of 26S rRNA m 5 C methylation by 35% (Fig. 1C). In the NL2099 strain, nsun-1 121 RNAi treatment also led to a reduction of 26S rRNA m 5 C methylation by 26% ( Fig. 1D). 122As there are only two known modified m 5 C residues on worm 26S rRNA, and since one of 123 them is introduced by NSUN-5 (Adamla et al., 2019; Schosserer et al., 2015), a complete loss 124 of NSUN-1 activity was expected to result in a 50% decrease...

show abstract

“…Inspired by previously described dietary interventions that are capable of extending lifespan in multiple species 47,74,75 , we wanted to investigate whether, instead of keeping animals on one bacterial diet their entire life, altering food exposure at critical life stages could affect overall lifespan. We asked whether these foods could alter lifespan without any previous generational exposure.…”

Section: Discussionmentioning

confidence: 99%

Bacterial diets differentially alter lifespan and healthspan trajectories inC. elegans

Stuhr

Curran

2020

Preprint

View full text Add to dashboard Cite

Diet is one of the more variable aspects in life due to the variety of options that organisms are exposed to in their natural habitats. In the laboratory, C. elegans are raised on bacterial monocultures, traditionally the E.coli B strain OP50, and spontaneously occurring microbial contaminants are removed to limit experimental variability because diet -including the presence of contaminants, can exert a potent influence over animal physiology. In order to diversify the menu available to culture C. elegans in the lab, we have isolated and cultured three such microbes: Methylobacterium, Xanthomonas, and Sphingomonas. The nutritional composition of these diets is unique, and when fed to C. elegans, can differentially alter multiple life history traits including development, reproduction, and metabolism. In light of the influence each diet has on specific physiological attributes, we comprehensively assessed the impact of these diets on animal health and devised a blueprint for utilizing different diet combinations over the lifespan, as a nutraceutical for optimal longevity. The expansion of the bacterial diet options to use in the laboratory will provide a critical tool to better understand the complexities of gene-diet interactions for health.C. elegans interact with a variety of bacterial species in their natural environment, including Proteobacteria, Bacteroidetes, Firmicutes, and Actinobacteria [20] These bacterial species have shaped many aspects of C. elegans biology that have become undetectable in the artificial laboratory environment [16,[19][20][21][22]. Here we expand the menu of bacterial diets for the study of gene-diet interactions which allows for further insight into the contribution diets have on C. elegans physiology [4,23]. Our studies provide a blueprint for how to use diet as a nutraceutical for manipulation of lifespan trajectories. genes altered in animals fed HT115/K-12, 3329 genes altered in animals fed HB101/B&K-12, 456 genes altered in animals fed Red/Methylobacterium diet, 1146 genes altered in animals fed Orange/Xanthomonas, and 5619 genes altered in animals fed Yellow/Sphingomonas. Of these, 100 genes were uniquely altered in animals fed the HT115/K-12 diet, 324 on the HB101/B&K-12 hybrid, 41 on the Red/Methylobacterium diet, 24 on the Orange/Xanthomonas diet, and strikingly 2421 on the Yellow/Sphingomonas diet (Figure 2G and supplementary file 1). In addition to finding genes that were shared on two, three, and four diet types, we also identified 140 genes that were altered on all five diets, as compared to OP50/B fed animals.An analysis of the Gene Ontology (GO)-terms of the unique genes that were differentially expressed in animals fed each bacteria type revealed specific molecular signatures for each diet (Figure 2H), as well as phenotypic profiles and cell/tissue enrichment (supplementary file 1) for each diet. Notably, we observed expression changes for genes that could alter multiple physiological processes including development, metabolism, reproduction, and aging. In considerat...

show abstract

Dietary restriction induces posttranscriptional regulation of longevity genes

Cited by 33 publications

References 135 publications

The ribosomal RNA m5C methyltransferase NSUN-1 modulates healthspan and oogenesis in Caenorhabditis elegans

The ribosomal RNA m5C methyltransferase NSUN-1 modulates healthspan and oogenesis in Caenorhabditis elegans

The ribosomal RNA m⁵C methyltransferase NSUN-1 modulates healthspan and oogenesis in Caenorhabditis elegans

Bacterial diets differentially alter lifespan and healthspan trajectories inC. elegans

Contact Info

Product

Resources

About