Similar Datasets
Project description:Genomes produce widespread long non-coding RNAs (lncRNAs) of largely unknown functions. We characterize aal1 (ageing-associated lncRNA), which is induced in quiescent fission yeast cells. Deletion of aal1 shortens the chronological lifespan of non-dividing cells, while ectopic overexpression prolongs their lifespan, indicating that aal1 acts in trans. Overexpression of aal1 represses ribosomal-protein gene expression and inhibits cell growth, and aal1 genetically interacts with coding genes functioning in protein translation. The aal1 lncRNA localizes to the cytoplasm and associates with ribosomes. Notably, aal1 overexpression decreases the cellular ribosome content and inhibits protein translation. The aal1 lncRNA binds to the rpl1901 mRNA, encoding a ribosomal protein. The rpl1901 levels are reduced ~2-fold by aal1, which is sufficient to extend lifespan. Remarkably, the expression of the aal1 lncRNA in Drosophila boosts fly lifespan. We propose that aal1 reduces the ribosome content by decreasing Rpl1901 levels, thus attenuating the translational capacity and promoting longevity. Although aal1 is not conserved, its effect in flies suggests that animals feature related mechanisms that modulate ageing, based on the conserved translational machinery.
| S-SCDT-10_1038-S44319-024-00265-9 | biostudies-other
Project description:Genomes pervasively produce long non-coding RNAs (lncRNAs) of largely unknown functions. Some of these lncRNAs have been implicated in roles related to ageing and associated diseases. Here we characterize aal1 (ageing-associated lncRNA 1) which is induced in non-dividing, ageing cells of fission yeast. Deletion of aal1 shortens the chronological lifespan of non-dividing cells, while ectopic overexpression of aal1 from a plasmid prolongs their lifespan, indicating that this lncRNA acts in trans. We find that aal1 genetically interacts with coding genes functioning in processes related to protein translation, and aal1 overexpression leads to repression of ribosomal protein genes and inhibition of cell growth. The aal1 RNA localizes to the cytoplasm and associates with ribosomes. Notably, aal1 deletion or overexpression is sufficient to increase or decrease the cellular ribosome content, respectively. We identify the mRNA rpl1901, encoding a ribosomal protein, as a binding target of aal1. The expression of rpl1901 is moderately repressed by aal1, and such moderate repression is critical and sufficient to extend the chronological lifespan. Remarkably, expression of the yeast aal1 lncRNA in the fly gut triggers a significant extension of the lifespan in flies. Based on these findings, we propose that the aal1 RNA can reduce the ribosome content by decreasing the levels of the Rpl1901 ribosomal protein, thus attenuating protein translation and promoting longevity. Although the aal1 lncRNA itself is not conserved, its effects in the fly raise the possibility that other organisms feature related mechanisms involving conserved ribosome-associated processes to control ageing.
2024-10-21 | GSE243034 | GEO
Project description:Genomes pervasively produce long non-coding RNAs (lncRNAs) of largely unknown functions. Some of these lncRNAs have been implicated in roles related to ageing and associated diseases. Here we characterize aal1 (ageing-associated lncRNA 1) which is induced in non-dividing, ageing cells of fission yeast. Deletion of aal1 shortens the chronological lifespan of non-dividing cells, while ectopic overexpression of aal1 from a plasmid prolongs their lifespan, indicating that this lncRNA acts in trans. We find that aal1 genetically interacts with coding genes functioning in processes related to protein translation, and aal1 overexpression leads to repression of ribosomal protein genes and inhibition of cell growth. The aal1 RNA localizes to the cytoplasm and associates with ribosomes. Notably, aal1 deletion or overexpression is sufficient to increase or decrease the cellular ribosome content, respectively. We identify the mRNA rpl1901, encoding a ribosomal protein, as a binding target of aal1. The expression of rpl1901 is moderately repressed by aal1, and such moderate repression is critical and sufficient to extend the chronological lifespan. Remarkably, expression of the yeast aal1 lncRNA in the fly gut triggers a significant extension of the lifespan in flies. Based on these findings, we propose that the aal1 RNA can reduce the ribosome content by decreasing the levels of the Rpl1901 ribosomal protein, thus attenuating protein translation and promoting longevity. Although the aal1 lncRNA itself is not conserved, its effects in the fly raise the possibility that other organisms feature related mechanisms involving conserved ribosome-associated processes to control ageing.
2024-10-21 | GSE243035 | GEO
Project description:Ageing-associated long non-coding RNA extends lifespan and reduces translation in non-dividing cells
| PRJNA1016255 | ENA
Project description:Ageing-associated long non-coding RNA extends lifespan and reduces translation in non-dividing cells [aal1OE_RNAseq]
| PRJNA1016254 | ENA
Project description:Ageing-associated long non-coding RNA extends lifespan and reduces translation in non-dividing cells [aal1_ChIRP-RNAseq]
| PRJNA1016262 | ENA
Project description:Protein synthesis is a regulated cellular process that links nutrients in the environment to organismal growth and development. Here we examine the role of genes that regulate mRNA translation in determining growth, reproduction, stress resistance and lifespan. Translational control of protein synthesis by regulators such as the cap-binding complex and S6 kinase play an important role during growth. We observe that inhibition of various genes in the translation initiation complex including ifg-1, the worm homologue of eIF4G, which is a scaffold protein in the cap-binding complex; and rsks-1, the worm homologue of S6 kinase, results in lifespan extension in Caenorhabditis elegans. Inhibition of ifg-1 or rsks-1 also slows development, reduces fecundity and increases resistance to starvation. A reduction in ifg-1 expression in dauers was also observed, suggesting an inhibition of protein translation during the dauer state. Thus, mRNA translation exerts pleiotropic effects on growth, reproduction, stress resistance and lifespan in C. elegans.
| S-EPMC2745345 | biostudies-literature
Project description:In Saccharomyces cerevisiae, deletion of large ribosomal subunit protein-encoding genes increases the replicative lifespan in a Gcn4-dependent manner. However, how Gcn4, a key transcriptional activator of amino acid biosynthesis genes, increases lifespan, is unknown. Here we show that Gcn4 acts as a repressor of protein synthesis. By analyzing the messenger RNA and protein abundance, ribosome occupancy and protein synthesis rate in various yeast strains, we demonstrate that Gcn4 is sufficient to reduce protein synthesis and increase yeast lifespan. Chromatin immunoprecipitation reveals Gcn4 binding not only at genes that are activated, but also at genes, some encoding ribosomal proteins, that are repressed upon Gcn4 overexpression. The promoters of repressed genes contain Rap1 binding motifs. Our data suggest that Gcn4 is a central regulator of protein synthesis under multiple perturbations, including ribosomal protein gene deletions, calorie restriction, and rapamycin treatment, and provide an explanation for its role in longevity and stress response.The transcription factor Gcn4 is known to regulate yeast amino acid synthesis. Here, the authors show that Gcn4 also acts as a repressor of protein biosynthesis in a range of conditions that enhance yeast lifespan, such as ribosomal protein knockout, calorie restriction or mTOR inhibition.
| S-EPMC5587724 | biostudies-literature
Project description:Aberrant protein aggregation and mitochondrial dysfunction have each been linked to aging and a number of age-onset neurodegenerative disorders, including Parkinson disease. Loss-of-function mutations in parkin, an E3 ubiquitin ligase that functions to promote the ubiquitin-proteasome system of protein degradation and also in mitochondrial quality control, have been implicated in heritable forms of Parkinson disease. The question of whether parkin can modulate aging or positively impact longevity, however, has not been addressed. Here, we show that ubiquitous or neuron-specific up-regulation of Parkin, in adult Drosophila melanogaster, increases both mean and maximum lifespan without reducing reproductive output, physical activity, or food intake. Long-lived Parkin-overexpressing flies display an increase in K48-linked polyubiquitin and reduced levels of protein aggregation during aging. Recent evidence suggests that Parkin interacts with the mitochondrial fission/fusion machinery to mediate the turnover of dysfunctional mitochondria. However, the relationships between parkin gene activity, mitochondrial dynamics, and aging have not been explored. We show that the mitochondrial fusion-promoting factor Drosophila Mitofusin, a Parkin substrate, increases in abundance during aging. Parkin overexpression results in reduced Drosophila Mitofusin levels in aging flies, with concomitant changes in mitochondrial morphology and an increase in mitochondrial activity. Together, these findings reveal roles for Parkin in modulating organismal aging and provide insight into the molecular mechanisms linking aging to neurodegeneration.
| S-EPMC3666724 | biostudies-literature
Project description:Methionine restriction (MetR) extends lifespan in various organisms, but its mechanistic understanding remains incomplete. Whether MetR during a specific period of adulthood increases lifespan is not known. In Drosophila, MetR is reported to extend lifespan only when amino acid levels are low. Here, by using an exome-matched holidic medium, we show that decreasing Met levels to 10% extends Drosophila lifespan with or without decreasing total amino acid levels. MetR during the first four weeks of adult life only robustly extends lifespan. MetR in young flies induces the expression of many longevity-related genes, including Methionine sulfoxide reductase A (MsrA), which reduces oxidatively-damaged Met. MsrA induction is foxo-dependent and persists for two weeks after cessation of the MetR diet. Loss of MsrA attenuates lifespan extension by early-adulthood MetR. Our study highlights the age-dependency of the organismal response to specific nutrients and suggests that nutrient restriction during a particular period of life is sufficient for healthspan extension.
| S-EPMC10698029 | biostudies-literature