Developmental regulation of canonical and small ORF translation from mRNAs

Background: Ribosomal profiling has revealed the translation of thousands of sequences outside annotated protein-coding genes, including small open reading frames of less than 100 codons, and the translational regulation of many genes. Here we present an improved version of Poly-Ribo-Seq and apply it to Drosophila melanogaster embryos to extend the catalog of in vivo translated small ORFs, and to reveal the translational regulation of both small and canonical ORFs from mRNAs across embryogenesis. Results: We obtain highly correlated samples across five embryonic stages, with nearly 500 million putative ribosomal footprints mapped to mRNAs, and compare them to existing Ribo-Seq and proteomic data. Our analysis reveals, for the first time in Drosophila, footprints mapping to codons in a phased pattern, the hallmark of productive translation. We propose a simple binomial probability metric to ascertain translation probability. Our results also reveal reproducible ribosomal binding apparently not resulting in productive translation. This non-productive ribosomal binding seems to be especially prevalent amongst upstream short ORFs located in the 5′ mRNA leaders, and amongst canonical ORFs during the activation of the zygotic translatome at the maternal-to zygotic transition. Conclusions: We suggest that this non-productive ribosomal binding might be due to cis-regulatory ribosomal binding and to defective ribosomal scanning of ORFs outside periods of productive translation. Our results are compatible with the main function of upstream short ORFs being to buffer the translation of canonical canonical ORFs; and show that, in general, small ORFs in mRNAs display markers compatible with an evolutionary transitory state towards full coding function

Magnetoestratigrafía del Cretácico Superior del sector Occidental de las Sierras Exteriores (Pirineo Occidental); implicaciones bioestratigráficas.

El Cretácico Superior del sector más Occidental de las Sierras Exteriores (Sa de Sto. Domingo) está escasamente representado en potencia pero presenta las facies más someras y transicionales donde se han recuperado recientemente restos de vertebrados fósiles (Osteichthyes, Chondrichthyes y Dinosauria), algunos de los cuales son de carácter continental. En este trabajo se presentan los resultados del análisis magnetoestratigráfico llevado a cabo en 4 secciones de pequeña potencia situadas entre los meridianos de San Felices y de Luesia (Prov. de Zaragoza). La magnetización característica de estas rocas es estable, primaria y muestra dos polaridades del campo magnético. La correlación tentativa entre perfiles, unida al conocimiento de las asociaciones de vertebrados existente en la cuenca de Graus-Tremp, permiten proponer una correlación preliminar que relacionaría los niveles fosilíferos con el cron C32n (Campaniense) y las facies Garum con los crones C29r, C29n y C28r (Maastrichtiense y Daniense) de la escala global de polaridad magnética. Esta correlación conlleva un hiato sedimentario durante el Maastrichtiense que deberá ser revisado en futuros estudios sedimentológicos

Dioxin Toxicity In Vivo Results from an Increase in the Dioxin-Independent Transcriptional Activity of the Aryl Hydrocarbon Receptor

The Aryl hydrocarbon receptor (Ahr) is the nuclear receptor mediating the toxicity of dioxins -widespread and persistent pollutants whose toxic effects include tumor promotion, teratogenesis, wasting syndrome and chloracne. Elimination of Ahr in mice eliminates dioxin toxicity but also produces adverse effects, some seemingly unrelated to dioxin. Thus the relationship between the toxic and dioxin-independent functions of Ahr is not clear, which hampers understanding and treatment of dioxin toxicity. Here we develop a Drosophila model to show that dioxin actually increases the in vivo dioxin-independent activity of Ahr. This hyperactivation resembles the effects caused by an increase in the amount of its dimerisation partner Ahr nuclear translocator (Arnt) and entails an increased transcriptional potency of Ahr, in addition to the previously described effect on nuclear translocation. Thus the two apparently different functions of Ahr, dioxin-mediated and dioxin-independent, are in fact two different levels (hyperactivated and basal, respectively) of a single function

Classification and function of small open reading frames

Small open reading frames (smORFs) of 100 codons or fewer are usually - if arbitrarily - excluded from proteome annotations. Despite this, the genomes of many metazoans, including humans, contain millions of smORFs, some of which fulfil key physiological functions. Recently, the transcriptome of Drosophila melanogaster was shown to contain thousands of smORFs of different classes that actively undergo translation, which produces peptides of mostly unknown function. Here, we present a comprehensive analysis of smORFs in flies, mice and humans. We propose the existence of several functional classes of smORFs, ranging from inert DNA sequences to transcribed and translated cis-regulators of translation and peptides with a propensity to function as regulators of membrane-associated proteins, or as components of ancient protein complexes in the cytoplasm. We suggest that the different smORF classes could represent steps in gene, peptide and protein evolution. Our analysis introduces a distinction between different peptide-coding classes of smORFs in animal genomes, and highlights the role of model organisms for the study of small peptide biology in the context of development, physiology and human disease

Functions of long non-coding RNAs in human disease and their conservation in Drosophila development

Genomic analysis has found that the transcriptome in both humans and Drosophila melanogaster features large numbers of long non-coding RNA transcripts (lncRNAs). This recently discovered class of RNAs regulates gene expression in diverse ways and has been involved in a large variety of important biological functions. Importantly, an increasing number of lncRNAs have also been associated with a range of human diseases, including cancer. Comparative analyses of their functions among these organisms suggest that some of their modes of action appear to be conserved. This highlights the importance of model organisms such as Drosophila, which shares many gene regulatory networks with humans, in understanding lncRNA function and its possible impact in human health. This review discusses some known functions and mechanisms of action of lncRNAs and their implication in human diseases, together with their functional conservation and relevance in Drosophila development

Expression of Distal-less, dachshund, and optomotor blind in Neanthes arenaceodentata (Annelida, Nereididae) does not support homology of appendage-forming mechanisms across the Bilateria

The similarity in the genetic regulation of arthropod and vertebrate appendage formation has been interpreted as the product of a plesiomorphic gene network that was primitively involved in bilaterian appendage development and co-opted to build appendages (in modern phyla) that are not historically related as structures. Data from lophotrochozoans are needed to clarify the pervasiveness of plesiomorphic appendage forming mechanisms. We assayed the expression of three arthropod and vertebrate limb gene orthologs, Distal-less (Dll), dachshund (dac), and optomotor blind (omb), in direct-developing juveniles of the polychaete Neanthes arenaceodentata. Parapodial Dll expression marks premorphogenetic notopodia and neuropodia, becoming restricted to the bases of notopodial cirri and to ventral portions of neuropodia. In outgrowing cephalic appendages, Dll activity is primarily restricted to proximal domains. Dll expression is also prominent in the brain. dac expression occurs in the brain, nerve cord ganglia, a pair of pharyngeal ganglia, presumed interneurons linking a pair of segmental nerves, and in newly differentiating mesoderm. Domains of omb expression include the brain, nerve cord ganglia, one pair of anterior cirri, presumed precursors of dorsal musculature, and the same pharyngeal ganglia and presumed interneurons that express dac. Contrary to their roles in outgrowing arthropod and vertebrate appendages, Dll, dac, and omb lack comparable expression in Neanthes appendages, implying independent evolution of annelid appendage development. We infer that parapodia and arthropodia are not structurally or mechanistically homologous (but their primordia might be), that Dll’s ancestral bilaterian function was in sensory and central nervous system differentiation, and that locomotory appendages possibly evolved from sensory outgrowths

Clinically Isolated Syndromes Suggestive of Multiple Sclerosis: An Optical Coherence Tomography Study

Background: Optical coherence tomography (OCT) is a simple, high-resolution technique to quantify the thickness of retinal nerve fiber layer (RNFL), which provides an indirect measurement of axonal damage in multiple sclerosis (MS). This study aimed to evaluate RNFL thickness in patients at presentation with clinically isolated syndromes (CIS) suggestive of MS. Methodology: This was a cross-sectional study. Twenty-four patients with CIS suggestive of MS (8 optic neuritis [ON], 6 spinal cord syndromes, 5 brainstem symptoms and 5 with sensory and other syndromes) were prospectively studied. The main outcome evaluated was RNFL thickness at CIS onset. Secondary objectives were to study the relationship between RNFL thickness and MRI criteria for disease dissemination in space (DIS) as well as the presence of oligoclonal bands in the cerebrospinal fluid. Principal Findings: Thirteen patients had decreased RNFL thickness in at least one quadrant. Mean RNFL thickness was 101.67±10.72 μm in retrobulbar ON eyes and 96.93±10.54 in unaffected eyes. Three of the 6 patients with myelitis had at least one abnormal quadrant in one of the two eyes. Eight CIS patients fulfilled DIS MRI criteria. The presence of at least one quadrant of an optic nerve with a RNFL thickness at a P<5% cut-off value had a sensitivity of 75% and a specificity of 56% for predicting DIS MRI. Conclusions: The findings from this study show that axonal damage measured by OCT is present in any type of CIS; even in myelitis forms, not only in ON as seen up to now. OCT can detect axonal damage in very early stages of disease and seems to have high sensitivity and moderate specificity for predicting DIS MRI. Studies with prospective long-term follow-up would be needed to establish the prognostic value of baseline OCT finding

Field study on the accumulation of trace elements by vegetables produced in the vicinity of abandoned pyrite mines

To evaluate the accumulation of trace elements (TE) by vegetables produced in the vicinity of abandoned pyrite mines, eighteen different small farms were selected near three mines from the Portuguese sector of the Iberian Pyrite Belt (Sao Domingos, Aljustrel and Lousal). Total and bioavailable As, Cu, Pb, and Zn concentrations were analyzed in the soils, and the same TE were analyzed in three different vegetables, lettuce (Lactuca sativa), coriander (Coriandrum sativum), and cabbage (Brassica oleracea), collected at the same locations. The soils were contaminated with As, Cu, Pb, and Zn, since their total concentrations exceeded the considered soil quality guideline values for plant production in the majority of the sampling sites. The maximum total concentrations for those TE were extremely high in some of the sampling sites (e.g. 1851 mg As kg(-1) in Sao Domingos, 1126 mg Cu kg(-1) in Aljustrel, 4946 mg Pb kg(-1) in Sao Domingos, and 1224 mg Zn kg(-1) in Aljustrel). However, the soils were mainly circumneutral, a factor that contributes to their low bioavailable fractions. As a result, generally, the plants contained levels of these elements characteristic of uncontaminated plants, and accumulation factors for all elements <1, typical of excluder plants. Furthermore, the estimated daily intake (EDI) for Cu and Zn, through the consumption of these vegetables, falls below the recommended upper limit for daily intake of these elements. The sampling site that stood out from the others was located at Sao Joao de Negrilhos (Aljustrel), where bioavailable Zn levels were higher, a consequence of the slight acidity of the soil. Therefore, the Zn content in vegetables was also higher, characteristic of contaminated plants, emphasizing the risk of Zn entering the human food chain via the consumption of crops produced on those soils. (C) 2013 Elsevier B.V. All rights reserved.info:eu-repo/semantics/publishedVersio