Modeling RNA loops using sequence homology and geometric constraints

Summary: RNA loop regions are essential structural elements of RNA molecules influencing both their structural and functional properties. We developed RLooM, a web application for homology-based modeling of RNA loops utilizing template structures extracted from the PDB. RLooM allows the insertion and replacement of loop structures of a desired sequence into an existing RNA structure. Furthermore, a comprehensive database of loops in RNA structures can be accessed through the web interface

C. difficile is overdiagnosed in adults and a commensal in infants

Clostridioides difficile is an urgent threat in hospital-acquired infections world-wide, yet the microbial composition associated with C. difficile, in particular in C. difficile infection (CDI) cases, remains poorly characterised. Here, we analysed 534 metagenomes from 10 publicly available CDI study populations. While we detected C. difficile in only 30% of CDI samples, multiple other toxigenic species capable of inducing CDI-like symptomatology were prevalent, raising concerns about CDI overdiagnosis. We further tracked C. difficile in 42,814 metagenomic samples from 253 public studies. We found that C. difficile prevalence, abundance and association with other bacterial species is age-dependent. In healthy adults, C. difficile is a rare taxon associated with an overall species richness reduction, while in healthy infants C. difficile is a common member of the gut microbiome and its presence is associated with a significant increase in species richness. More specifically, we identified a group of species co-occurring with C. difficile exclusively in healthy infants, enriched in obligate anaerobes and in species typically found in the gut microbiome of healthy adults. Overall, gut microbiome composition in presence of C. difficile in healthy infants is associated with multiple parameters linked to a healthy gut microbiome maturation towards an adult-like state. Our results suggest that C. difficile is a commensal in infants, and that its asymptomatic carriage is dependent on the surrounding microbial context

Sequence–structure relationships in yeast mRNAs

It is generally accepted that functionally important RNA structure is more conserved than sequence due to compensatory mutations that may alter the sequence without disrupting the structure. For small RNA molecules sequence–structure relationships are relatively well understood. However, structural bioinformatics of mRNAs is still in its infancy due to a virtual absence of experimental data. This report presents the first quantitative assessment of sequence–structure divergence in the coding regions of mRNA molecules based on recently published transcriptome-wide experimental determination of their base paring patterns. Structural resemblance in paralogous mRNA pairs quickly drops as sequence identity decreases from 100% to 85–90%. Structures of mRNAs sharing sequence identity below roughly 85% are essentially uncorrelated. This outcome is in dramatic contrast to small functional non-coding RNAs where sequence and structure divergence are correlated at very low levels of sequence similarity. The fact that very similar mRNA sequences can have vastly different secondary structures may imply that the particular global shape of base paired elements in coding regions does not play a major role in modulating gene expression and translation efficiency. Apparently, the need to maintain stable three-dimensional structures of encoded proteins places a much higher evolutionary pressure on mRNA sequences than on their RNA structures

proGenomes3: approaching one million accurately and consistently annotated high-quality prokaryotic genomes

The interpretation of genomic, transcriptomic and other microbial 'omics data is highly dependent on the availability of well-annotated genomes. As the number of publicly available microbial genomes continues to increase exponentially, the need for quality control and consistent annotation is becoming critical. We present proGenomes3, a database of 907 388 high-quality genomes containing 4 billion genes that passed stringent criteria and have been consistently annotated using multiple functional and taxonomic databases including mobile genetic elements and biosynthetic gene clusters. proGenomes3 encompasses 41 171 species-level clusters, defined based on universal single copy marker genes, for which pan-genomes and contextual habitat annotations are provided. The database is available at http://progenomes.embl.de/

Detection and characterization of 3D-signature phosphorylation site motifs and their contribution towards improved phosphorylation site prediction in proteins

<p>Abstract</p> <p>Background</p> <p>Phosphorylation of proteins plays a crucial role in the regulation and activation of metabolic and signaling pathways and constitutes an important target for pharmaceutical intervention. Central to the phosphorylation process is the recognition of specific target sites by protein kinases followed by the covalent attachment of phosphate groups to the amino acids serine, threonine, or tyrosine. The experimental identification as well as computational prediction of phosphorylation sites (P-sites) has proved to be a challenging problem. Computational methods have focused primarily on extracting predictive features from the local, one-dimensional sequence information surrounding phosphorylation sites.</p> <p>Results</p> <p>We characterized the spatial context of phosphorylation sites and assessed its usability for improved phosphorylation site predictions. We identified 750 non-redundant, experimentally verified sites with three-dimensional (3D) structural information available in the protein data bank (PDB) and grouped them according to their respective kinase family. We studied the spatial distribution of amino acids around phosphorserines, phosphothreonines, and phosphotyrosines to extract signature 3D-profiles. Characteristic spatial distributions of amino acid residue types around phosphorylation sites were indeed discernable, especially when kinase-family-specific target sites were analyzed. To test the added value of using spatial information for the computational prediction of phosphorylation sites, Support Vector Machines were applied using both sequence as well as structural information. When compared to sequence-only based prediction methods, a small but consistent performance improvement was obtained when the prediction was informed by 3D-context information.</p> <p>Conclusion</p> <p>While local one-dimensional amino acid sequence information was observed to harbor most of the discriminatory power, spatial context information was identified as relevant for the recognition of kinases and their cognate target sites and can be used for an improved prediction of phosphorylation sites. A web-based service (Phos3D) implementing the developed structure-based P-site prediction method has been made available at <url>http://phos3d.mpimp-golm.mpg.de</url>.</p

It's a loop world – single strands in RNA as structural and functional elements

Unpaired regions in RNA molecules – loops – are centrally involved in defining the characteristic three-dimensional (3D) architecture of RNAs and are of high interest in RNA engineering and design. Loops adopt diverse, but specific conformations stabilised by complex tertiary structural interactions that provide structural flexibility to RNA structures that would otherwise not be possible if they only consisted of the rigid A-helical shapes usually formed by canonical base pairing. By participating in sequence-non-local contacts, they furthermore contribute to stabilising the overall fold of RNA molecules. Interactions between RNAs and other nucleic acids, proteins, or small molecules are also generally mediated by RNA loop structures. Therefore, the function of an RNA molecule is generally dependent on its loops. Examples include intermolecular interactions between RNAs as part of the microRNA processing pathways, ribozymatic activity, or riboswitch-ligand interactions. Bioinformatics approaches have been successfully applied to the identification of novel RNA structural motifs including loops, local and global RNA 3D structure prediction, and structural and conformational analysis of RNAs and have contributed to a better understanding of the sequence-structure-function relationships in RNA loops

Quality targets for active ingredients of pesticides to protect inland surface waters

SIGLEAvailable from TIB Hannover: RN 8422(2001,8) / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekDEGerman

Zielvorgaben fuer Pflanzenschutzmittelwirkstoffe zum Schutz oberirdischer Binnengewaesser

Available from TIB Hannover: RN 8422(1999,76) / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEDEGerman

Convergent Loss of an EDS1/PAD4 Signaling Pathway in Several Plant Lineages Reveals Coevolved Components of Plant Immunity and Drought Response

Plant innate immunity relies on nucleotide binding leucine-rich repeat receptors (NLRs) that recognize pathogen-derived molecules and activate downstream signaling pathways. We analyzed the variation in NLR gene copy number and identified plants with a low number of NLR genes relative to sister species. We specifically focused on four plants from two distinct lineages, one monocot lineage (Alismatales) and one eudicot lineage (Lentibulariaceae). In these lineages, the loss of NLR genes coincides with loss of the well-known downstream immune signaling complex ENHANCED DISEASE SUSCEPTIBILITY 1 (EDS1)/PHYTOALEXIN DEFICIENT 4 (PAD4). We expanded our analysis across whole proteomes and found that other characterized immune genes were absent only in Lentibulariaceae and Alismatales. Additionally, we identified genes of unknown function that were convergently lost together with EDS1/PAD4 in five plant species. Gene expression analyses in Arabidopsis (Arabidopsis thaliana) and Oryza sativa revealed that several homologs of the candidates are differentially expressed during pathogen infection, drought, and abscisic acid treatment. Our analysis provides evolutionary evidence for the rewiring of plant immunity in some plant lineages, as well as the coevolution of the EDS1/PAD4 pathway and drought responses