58 research outputs found

    SAMMSON fosters cancer cell fitness by concertedly enhancing mitochondrial and cytosolic translation

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    Synchronization of mitochondrial and cytoplasmic translation rates is critical for the maintenance of cellular fitness, with cancer cells being especially vulnerable to translational uncoupling. Although alterations of cytosolic protein synthesis are common in human cancer, compensating mechanisms in mitochondrial translation remain elusive. Here we show that the malignant long non-coding RNA (lncRNA) SAMMSON promotes a balanced increase in ribosomal RNA (rRNA) maturation and protein synthesis in the cytosol and mitochondria by modulating the localization of CARF, an RNA-binding protein that sequesters the exo-ribonuclease XRN2 in the nucleoplasm, which under normal circumstances limits nucleolar rRNA maturation. SAMMSON interferes with XRN2 binding to CARF in the nucleus by favoring the formation of an aberrant cytoplasmic RNA-protein complex containing CARF and p32, a mitochondrial protein required for the processing of the mitochondrial rRNAs. These data highlight how a single oncogenic lncRNA can simultaneously modulate RNA-protein complex formation in two distinct cellular compartments to promote cell growth

    Specialized box C/D snoRNPs act as antisense guides to target RNA base acetylation

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    Box C/D snoRNAs are known to guide site-specific ribose methylation of ribosomal RNA. Here, we demonstrate a novel and unexpected role for box C/D snoRNAs in guiding 18S rRNA acetylation in yeast. Our results demonstrate, for the first time, that the acetylation of two cytosine residues in 18S rRNA catalyzed by Kre33 is guided by two orphan box C/D snoRNAs–snR4 and snR45 –not known to be involved in methylation in yeast. We identified Kre33 binding sites on these snoRNAs as well as on the 18S rRNA, and demonstrate that both snR4 and snR45 establish extended bipartite complementarity around the cytosines targeted for acetylation, similar to pseudouridylation pocket formation by the H/ACA snoRNPs. We show that base pairing between these snoRNAs and 18S rRNA requires the putative helicase activity of Kre33, which is also needed to aid early pre-rRNA processing. Compared to yeast, the number of orphan box C/D snoRNAs in higher eukaryotes is much larger and we hypothesize that several of these may be involved in base-modifications

    AVONET: morphological, ecological and geographical data for all birds

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    Functional traits offer a rich quantitative framework for developing and testing theories in evolutionary biology, ecology and ecosystem science. However, the potential of functional traits to drive theoretical advances and refine models of global change can only be fully realised when species‐level information is complete. Here we present the AVONET dataset containing comprehensive functional trait data for all birds, including six ecological variables, 11 continuous morphological traits, and information on range size and location. Raw morphological measurements are presented from 90,020 individuals of 11,009 extant bird species sampled from 181 countries. These data are also summarised as species averages in three taxonomic formats, allowing integration with a global phylogeny, geographical range maps, IUCN Red List data and the eBird citizen science database. The AVONET dataset provides the most detailed picture of continuous trait variation for any major radiation of organisms, offering a global template for testing hypotheses and exploring the evolutionary origins, structure and functioning of biodiversity

    Yeast 18S rRNA Dimethylase Dim1p: a Quality Control Mechanism in Ribosome Synthesis?

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    One of the few rRNA modifications conserved between bacteria and eukaryotes is the base dimethylation present at the 3â€Č end of the small subunit rRNA. In the yeast Saccharomyces cerevisiae, this modification is carried out by Dim1p. We previously reported that genetic depletion of Dim1p not only blocked this modification but also strongly inhibited the pre-rRNA processing steps that lead to the synthesis of 18S rRNA. This prevented the formation of mature but unmodified 18S rRNA. The processing steps inhibited were nucleolar, and consistent with this, Dim1p was shown to localize mostly to this cellular compartment. dim1-2 was isolated from a library of conditionally lethal alleles of DIM1. In dim1-2 strains, pre-rRNA processing was not affected at the permissive temperature for growth, but dimethylation was blocked, leading to strong accumulation of nondimethylated 18S rRNA. This demonstrates that the enzymatic function of Dim1p in dimethylation can be separated from its involvement in pre-rRNA processing. The growth rate of dim1-2 strains was not affected, showing the dimethylation to be dispensable in vivo. Extracts of dim1-2 strains, however, were incompetent for translation in vitro. This suggests that dimethylation is required under the suboptimal in vitro conditions but only fine-tunes ribosomal function in vivo. Unexpectedly, when transcription of pre-rRNA was driven by a polymerase II PGK promoter, its processing became insensitive to temperature-sensitive mutations in DIM1 or to depletion of Dim1p. This observation, which demonstrates that Dim1p is not directly required for pre-rRNA processing reactions, is consistent with the inhibition of pre-rRNA processing by an active repression system in the absence of Dim1p

    The DIM1 gene responsible for the conserved m6(2)Am6(2)A dimethylation in the 3'-terminal loop of 18 S rRNA is essential in yeast.

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    Biogenesis of cytoplasmic ribosomes universally involves methylation of ribosomal RNA. Little genetic evidence is available about the functional role(s) of this conserved posttranscriptional modification. The only known methylase gene involved in rRNA maturation is ksgA in Escherichia coli, which directs dimethylation of two adjacent adenosines (m6(2)A1518m6(2)A1519) in the loop of a conserved hairpin near the 3'-end of 16 S rRNA. This tandem methylation is the only rRNA modification common to pro and eukaryotes. Disruption of ksgA confers resistance to the aminoglycoside antibiotic kasugamycin without significantly impairing viability. Here we report the cloning of the DIM1 gene encoding the homolog 18 S rRNA dimethylase in Saccharomyces cerevisiae. The yeast enzyme is evolutionary related to the ksgA protein. It carries a distinctive lysine-rich-N-terminal extension with a potential protein kinase C phosphorylation site. Like ksgA, DIM1 belongs to the erm family of prokaryotic 23 S rRNA dimethylases responsible for erythromycin resistance. Surprisingly, disruption of DIM1 turns out to be lethal in yeast.Journal Articleinfo:eu-repo/semantics/publishe

    Differential Gene Expression Correlates with Behavioural Polymorphism during Collective Behaviour in Cockroaches

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    Consistent inter-individual variation in the propensity to perform different tasks (animal personality) can contribute significantly to the success of group-living organisms. The distribution of different personalities in a group influences collective actions and therefore how these organisms interact with their environment. However, we have little understanding of the proximate mechanisms underlying animal personality in animal groups, and research on this theme has often been biased towards organisms with advanced social systems. The goal of this study is to investigate the mechanistic basis for personality variation during collective behaviour in a species with rudimentary societies: the American cockroach. We thus use an approach which combines experimental classification of individuals into behavioural phenotypes (‘bold’ and ‘shy’ individuals) with comparative gene expression. Our analyses reveal differences in gene expression between behavioural phenotypes and suggest that social context may modulate gene expression related to bold/shy characteristics. We also discuss how cockroaches could be a valuable model for the study of genetic mechanisms underlying the early steps in the evolution of social behaviour and social complexity. This study provides a first step towards a better understanding of the molecular mechanisms associated with differences in boldness and behavioural plasticity in these organisms

    Pseudouridine Mapping in the Saccharomyces cerevisiae Spliceosomal U Small Nuclear RNAs (snRNAs) Reveals that Pseudouridine Synthase Pus1p Exhibits a Dual Substrate Specificity for U2 snRNA and tRNA

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    Pseudouridine (Κ) residues were localized in the Saccharomyces cerevisiae spliceosomal U small nuclear RNAs (UsnRNAs) by using the chemical mapping method. In contrast to vertebrate UsnRNAs, S. cerevisiae UsnRNAs contain only a few Κ residues, which are located in segments involved in intermolecular RNA-RNA or RNA-protein interactions. At these positions, UsnRNAs are universally modified. When yeast mutants disrupted for one of the several pseudouridine synthase genes (PUS1, PUS2, PUS3, and PUS4) or depleted in rRNA-pseudouridine synthase Cbf5p were tested for UsnRNA Κ content, only the loss of the Pus1p activity was found to affect Κ formation in spliceosomal UsnRNAs. Indeed, Κ(44) formation in U2 snRNA was abolished. By using purified Pus1p enzyme and in vitro-produced U2 snRNA, Pus1p is shown here to catalyze Κ(44) formation in the S. cerevisiae U2 snRNA. Thus, Pus1p is the first UsnRNA pseudouridine synthase characterized so far which exhibits a dual substrate specificity, acting on both tRNAs and U2 snRNA. As depletion of rRNA-pseudouridine synthase Cbf5p had no effect on UsnRNA Κ content, formation of Κ residues in S. cerevisiae UsnRNAs is not dependent on the Cbf5p-snoRNA guided mechanism
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