The role of non-standard translation in Candida albicans pathogenesis.

Candida albicans typically resides in the human gastrointestinal tract and mucosal membranes as a commensal organism. To adapt and cope with the host immune system, it has evolved a variety of mechanisms of adaptation such as stress-induced mutagenesis and epigenetic regulation. Niche-specific patterns of gene expression also allow the fungus to fine-tune its response to specific microenvironments in the host and switch from harmless commensal to invasive pathogen. Proteome plasticity produced by CUG ambiguity, on the other hand is emerging as a new layer of complexity in C. albicans adaptation, pathogenesis, and drug resistance. Such proteome plasticity is the result of a genetic code alteration where the leucine CUG codon is translated mainly as serine (97%), but maintains some level of leucine (3%) assignment. In this review, we dissect the link between C. albicans non-standard CUG translation, proteome plasticity, host adaptation and pathogenesis. We discuss published work showing how this pathogen uses the fidelity of protein synthesis to spawn novel virulence traits.

tRNAs as a Driving Force of Genome Evolution in Yeast.

Transfer RNAs (tRNAs) are widely known for their roles in the decoding of the linear mRNA information into amino acid sequences of proteins. They are also multifunctional platforms in the translation process and have other roles beyond translation, including sensing amino acid abundance, interacting with the general stress response machinery, and modulating cellular adaptation, survival, and death. In this mini-review, we focus on the emerging role of tRNA genes in the organization and modification of the genomic architecture of yeast and the role of tRNA misexpression and decoding infidelity in genome stability, evolution, and adaption. We discuss published work showing how quickly tRNA genes can mutate to meet novel translational demands, how tRNAs speed up genome evolution, and how tRNA genes can be sites of genomic instability. We highlight recent works showing that loss of tRNA decoding fidelity and small alterations in tRNA expression have unexpected and profound impacts on genome stability. By dissecting these recent evidence, we hope to lay the groundwork that prompts future investigations on the mechanistic interplay between tRNAs and genome modification that likely triggers genome evolution.

Candida Species (Volatile) Metabotyping through Advanced Comprehensive Two-Dimensional Gas Chromatography.

Microbial metabolomics is a challenge strategy that allows a comprehensive analysis of metabolites within a microorganism and may support a new approach in microbial research, including the microbial diagnosis. Thus, the aim of this research was to in-depth explore a metabolomics strategy based on the use of an advanced multidimensional gas chromatography for the comprehensive mapping of cellular metabolites of C. albicans and non-C. albicans (C. glabrata and C. tropicalis) and therefore contributing for the development of a comprehensive platform for fungal detection management and for species distinction in early growth times (6 h). The volatile fraction comprises 126 putatively identified metabolites distributed over several chemical families: acids, alcohols, aldehydes, hydrocarbons, esters, ketones, monoterpenic and sesquiterpenic compounds, norisoprenoids, phenols and sulphur compounds. These metabolites may be related with different metabolic pathways, such as amino acid metabolism and biosynthesis, fatty acids metabolism, aromatic compounds degradation, mono and sesquiterpenoid synthesis and carotenoid cleavage. These results represent an enlargement of ca. 70% of metabolites not previously reported for C. albicans, 91% for C. glabrata and 90% for C. tropicalis. This study represents the most detailed study about Candida species exometabolome, allowing a metabolomic signature of each species, which signifies an improvement towards the construction of a Candida metabolomics platform whose application in clinical diagnostics can be crucial to guide therapeutic interventions.

Dre-miR-2188 targets Nrp2a and mediates proper intersegmental vessel development in zebrafish embryos.

BACKGROUND: MicroRNAs (miRNAs) are a class of small RNAs that are implicated in the control of eukaryotic gene expression by binding to the 3'UTR of target mRNAs. Several algorithms have been developed for miRNA target prediction however, experimental validation is still essential for the correct identification of miRNA targets. We have recently predicted that Neuropilin2a (Nrp2a), a vascular endothelial growth factor receptor which is essential for normal developmental angiogenesis in zebrafish, is a dre-miR-2188 target. METHODOLOGY: Here we show that dre-miR-2188 targets the 3'-untranslated region (3'UTR) of Nrp2a mRNA and is implicated in proper intersegmental vessel development in vivo. Over expression of miR-2188 in zebrafish embryos down regulates Nrp2a expression and results in intersegmental vessel disruption, while its silencing increases Nrp2a expression and intersegmental vessel sprouting. An in vivo GFP sensor assay based on a fusion between the GFP coding region and the Nrp2a 3'UTR confirms that miR-2188 binds to the 3'UTR of Nrp2a and inhibits protein translation. CONCLUSIONS: We demonstrate that miR-2188 targets Nrp2a and affects intersegmental vessel development in zebrafish embryos.

Ethanol exposure induces upregulation of specific microRNAs in zebrafish embryos.

Prenatal exposure to ethanol leads to a myriad of developmental disorders known as fetal alcohol spectrum disorder, often characterized by growth and mental retardation, central nervous system damage, and specific craniofacial dysmorphic features. The mechanisms of ethanol toxicity are not fully understood, but exposure during development affects the expression of several genes involved in cell cycle control, apoptosis, and transcriptional regulation. MicroRNAs (miRNAs) are implicated in some of these processes, however, it is not yet clear if they are involved in ethanol-induced toxicity. In order to clarify this question, we have exposed zebrafish embryos to ethanol and evaluated whether a miRNA deregulation signature could be obtained. Zebrafish embryos were exposed to 1 and 1.5% of ethanol from 4 h postfertilization (hpf) to 24 hpf. The miRNA expression profiles obtained reveal significant miRNA deregulation and show that both ethanol concentrations upregulate miR-153a, miR-725, miR-30d, let-7k, miR-100, miR-738, and miR-732. Putative gene targets of deregulated miRNAs are involved in cell cycle control, apoptosis, and transcription, which are the main processes affected by ethanol toxicity. The conservation of affected mechanisms among vertebrates leads us to postulate that similar miRNA deregulation occurs in humans, highlighting a relevant role of miRNAs in ethanol toxicology.