Ribosome heterogeneity in tumorigenesis: the rRNA point of view.
Ontology highlight
ABSTRACT:
SUBMITTER: Marcel V
PROVIDER: S-EPMC4905297 | biostudies-other | 2015 Jul-Sep
REPOSITORIES: biostudies-other
Similar Datasets
Project description:Ribosome heterogeneity is of increasing biological significance and several examples have been described for multicellular and single cells organisms. In here we show for the first time a variation in ribose methylation within the 18S rRNA of Saccharomyces cerevisiae. Using RNA-cleaving DNAzymes, we could specifically demonstrate that a significant amount of S. cerevisiae ribosomes are not methylated at 2'-O-ribose of A100 residue in the 18S rRNA. Furthermore, using LC-UV-MS/MS of a respective 18S rRNA fragment, we could not only corroborate the partial methylation at A100, but could also quantify the methylated versus non-methylated A100 residue. Here, we exhibit that only 68% of A100 in the 18S rRNA of S.cerevisiae are methylated at 2'-O ribose sugar. Polysomes also contain a similar heterogeneity for methylated Am100, which shows that 40S ribosome subunits with and without Am100 participate in translation. Introduction of a multicopy plasmid containing the corresponding methylation guide snoRNA gene SNR51 led to an increased A100 methylation, suggesting the cellular snR51 level to limit the extent of this modification. Partial rRNA modification demonstrates a new level of ribosome heterogeneity in eukaryotic cells that might have substantial impact on regulation and fine-tuning of the translation process.
| S-EPMC3938493 | biostudies-literature
Project description:Cancers of various organs have been categorized into distinct subtypes after increasingly sophisticated taxonomies. Additionally, within a seemingly homogeneous subclass, individual cancers contain diverse tumour cell populations that vary in important cancer-specific traits such as clonogenicity and invasive potential. Differences that exist between and within a given tumour type have hampered significantly both the proper selection of patients that might benefit from therapy, as well as the development of new targeted agents. In this review, we discuss the differences associated with organ-specific cancer subtypes and the factors that contribute to intra-tumour heterogeneity. It is of utmost importance to understand the biological causes that distinguish tumours as well as distinct tumour cell populations within malignancies, as these will ultimately point the way to more rational anti-cancer treatments.
| S-EPMC3736134 | biostudies-other
Project description:5S rRNA is an indispensable component of cytoplasmic ribosomes in all species. The functions of 5S rRNA and the reasons for its evolutionary preservation as an independent molecule remain unclear. Here we used ribosome engineering to investigate whether 5S rRNA autonomy is critical for ribosome function and cell survival. By linking circularly permutated 5S rRNA with 23S rRNA we generated a bacterial strain devoid of free 5S rRNA. Viability of the engineered cells demonstrates that autonomous 5S rRNA is dispensable for cell growth under standard conditions and is unlikely to have essential functions outside the ribosome. The fully assembled ribosomes carrying 23S-5S rRNA are highly active in translation. However, the engineered cells accumulate aberrant 50S subunits unable to form stable 70S ribosomes. Cryo-EM analysis revealed a malformed peptidyl transferase center in the misassembled 50S subunits. Our results argue that the autonomy of 5S rRNA is preserved due to its role in ribosome biogenesis.
| S-EPMC7283268 | biostudies-literature
Project description:Pharmacogenomics, a fascinating, emerging area of biomedical research is strongly influenced by growing availability of genomic databases, high-throughput genomic technologies, bioinformatic tools and artificial computational modelling approaches. One main area of pharmacogenomics is the discovery of new drugs and drug targets with molecular genetic, genomic or even bioinformatic methods; the other is the study of how genomic differences influence the variability in patients' responses to drugs. From a genetic point of view, asthma is multifactorial, which means that the susceptibility to the disease is determined by interactions between multiple genes, and involves important non-genetic factors such as the environment for their expression. In this review, we summarize collective evidence from linkage and association studies that have consistently reported suggestive linkage or association of asthma or its associated phenotypes to polymorphic markers and single nucleotide polymorphisms in selected chromosomes. Genes that have been found implicated in the disease are potential new drug targets and several pharmacological investigations are underway to utilize these new discoveries. Next, we will focus on the inter-individual variability in anti-asthmatic drug responses and review the recent results in this topic.
| S-EPMC2438267 | biostudies-literature
Project description:Annual flu seasons are typically characterized by changes in types and subtypes of influenza, with variations in terms of severity. Despite remarkable improvements in the prevention and management of patients with suspected or laboratory-confirmed diagnosis of influenza, annual seasonal influenza continues to be associated with a high morbidity and mortality. Admission to the intensive care unit is required for patients with severe forms of seasonal influenza infection, with primary pneumonia being present in most of the cases. This review summarizes the most recent knowledge on the diagnosis and treatment strategies in critically ill patients with influenza, focused on diagnostic testing methods, antiviral therapy, use of corticosteroids, antibacterial and antifungal therapy, and supportive measures. The review focuses on diagnostic testing methods, antiviral therapy, use of corticosteroids, antibacterial and antifungal therapy, supportive measures and relevant existing evidence, in order to provide the non-expert clinician a useful overview. An enhanced understanding of current diagnostic and treatment aspects of influenza infection can contribute to improve outcomes and reduce mortality among ICU patients with influenza.
| S-EPMC7095473 | biostudies-literature
Project description:Ribose methylation is one of the two most abundant modifications in human ribosomal RNA and is believed to be important for ribosome biogenesis, mRNA selectivity and translational fidelity. We have applied RiboMeth-seq to rRNA from HeLa cells for ribosome-wide, quantitative mapping of 2'-O-Me sites and obtained a comprehensive set of 106 sites, including two novel sites, and with plausible box C/D guide RNAs assigned to all but three sites. We find approximately two-thirds of the sites to be fully methylated and the remainder to be fractionally modified in support of ribosome heterogeneity at the level of RNA modifications. A comparison to HCT116 cells reveals similar 2'-O-Me profiles with distinct differences at several sites. This study constitutes the first comprehensive mapping of 2'-O-Me sites in human rRNA using a high throughput sequencing approach. It establishes the existence of a core of constitutively methylated positions and a subset of variable, potentially regulatory positions, and paves the way for experimental analyses of the role of variations in rRNA methylation under different physiological or pathological settings.
| S-EPMC5027482 | biostudies-literature
Project description:A pyrogen is a substance that causes fever after intravenous administration or inhalation. Gram negative endotoxins are the most important pyrogens to pharmaceutical laboratories. In the International, United States, Japanese and European Pharmacopoeias, there are two official methods to evaluate pyrogenicitythat is, the bacterial endotoxin test, and the pyrogen test. The main objective of this review is to compare the monographs of each test among the different Pharmacopeias, to detect similarities and differences. The former can be considered fully harmonized, and only non-significant differences were detected. The latter, which is the only available assay for some products and formulations to demonstrate apyrogenicity, shows large differences, which should be considered.
| S-EPMC6115822 | biostudies-other
Project description:rRNAs are extensively modified during their transcription and subsequent maturation in the nucleolus, nucleus and cytoplasm. RNA modifications, which are installed either by snoRNA-guided or by stand-alone enzymes, generally stabilize the structure of the ribosome. However, they also cluster at functionally important sites of the ribosome, such as the peptidyltransferase center and the decoding site, where they facilitate efficient and accurate protein synthesis. The recent identification of sites of substoichiometric 2'-O-methylation and pseudouridylation has overturned the notion that all rRNA modifications are constitutively present on ribosomes, highlighting nucleotide modifications as an important source of ribosomal heterogeneity. While the mechanisms regulating partial modification and the functions of specialized ribosomes are largely unknown, changes in the rRNA modification pattern have been observed in response to environmental changes, during development, and in disease. This suggests that rRNA modifications may contribute to the translational control of gene expression.
| S-EPMC5699541 | biostudies-literature
Project description:During the recent decades significant improvements in the understanding of laryngeal molecular biology allowed a better characterization of the tumor. However, despite increased molecular knowledge and clinical efforts, survival of patients with laryngeal cancer remains the same as 30 years ago. Although this result may not make major conclusions as preservation approaches were not broadly used until the time of database collection, it seems to be clear that there is still window for improvement. Although the cornerstone for laryngeal cancer eradication is to implement smoking cessation programs, survival progresses will be hopefully seen in the future. Introducing molecular biomarkers as predictive factors to determine which patients will benefit of preservation treatments may become one of the next steps to improve survival. Furthermore, the development of new therapeutic modalities joint to biomarkers to selectively apply such new therapy in these patients may help to define new modalities with improved survival. New inhibitors against Notch pathway, EGFR, VRK1 or DNA damage repair may become gold standard if we are able to identify patients that may benefit from them, either on survival or functional larynx preservation. It is the moment for an inflexion point on the way laryngeal cancer is clinically managed.
| S-EPMC4894505 | biostudies-other
Project description:Oral lichen planus (OLP) is a chronic disease of uncertain etiology, although it is generally considered as an immune-mediated disease that affects the mucous membranes and even the skin and nails. Over the years, this disease was attributed to a variety of causes, including different types of microorganisms. This review analyzes the present state of the art of the disease, from a microbiological point of view, while considering whether or not the possibility of a microbial origin for the disease can be supported. From the evidence presented here, OLP should be considered an immunological disease, as it was initially proposed, as opposed to an illness of microbiological origin. The different microorganisms so far described as putative disease-causing agents do not fulfill Koch’s postulates; they are, actually, not the cause, but a result of the disease that provides the right circumstances for microbial colonization. This means that, at this stage, and unless new data becomes available, no microorganism can be envisaged as the causative agent of lichen planus.
| S-EPMC7943413 | biostudies-literature