TL;DR: An update of the Clusters of Orthologous Groups of proteins, the first since 2003, and a comprehensive revision of the COG annotations and expansion of the genome coverage to include representative complete genomes from all bacterial and archaeal lineages down to the genus level are presented.
Abstract: Microbial genome sequencing projects produce numerous sequences of deduced proteins, only a small fraction of which have been or will ever be studied experimentally. This leaves sequence analysis as the only feasible way to annotate these proteins and assign to them tentative functions. The Clusters of Orthologous Groups of proteins (COGs) database (http://www.ncbi.nlm.nih.gov/COG/), first created in 1997, has been a popular tool for functional annotation. Its success was largely based on (i) its reliance on complete microbial genomes, which allowed reliable assignment of orthologs and paralogs for most genes;(ii)orthology-basedapproach,whichusedthe function(s)ofthecharacterizedmember(s)oftheprotein family (COG) to assign function(s) to the entire set of carefully identified orthologs and describe the range of potential functions when there were more than one; and (iii) careful manual curation of the annotation of the COGs, aimed at detailed prediction of the biological function(s) for each COG while avoiding annotation errors and overprediction. Here we present an update of the COGs, the first since 2003, and a comprehensive revision of the COG annotations and expansion of the genome coverage to include representative complete genomes from all bacterial and archaeal lineages down to the genus level. This re-analysis of the COGs shows that the original COG assignments had an error rate below 0.5% and allows an assessment of the progress in functional genomics in the past 12 years. During this time, functions of many previously uncharacterized COGs have been elucidated and tentative functional assignments of many COGs have been validated, either by targeted experiments or through the use of high-throughput methods. A particularly important development is the assignment of functions to several widespread, conserved proteins many of which turned out to participate in translation, in particular rRNA maturation and tRNA modification. The new version of the COGs is expected to become an important tool for microbial genomics.
TL;DR: New features are included: a census of human and yeast snoRNAs involved in RNA-guided RNA modification, a new section covering the 5′-end capping process, and a catalogue of ‘building blocks’ for chemical synthesis of a large variety of modified nucleosides.
Abstract: MODOMICS is a database of RNA modifications that provides comprehensive information concerning the chemical structures of modified ribonucleosides, their biosynthetic pathways, RNA-modifying enzymes and location of modified residues in RNA sequences. In the current database version, accessible at http://modomics.genesilico.pl, we included new features: a census of human and yeast snoRNAs involved in RNA-guided RNA modification, a new section covering the 5′-end capping process, and a catalogue of ‘building blocks’ for chemical synthesis of a large variety of modified nucleosides. The MODOMICS collections of RNA modifications, RNA-modifying enzymes and modified RNAs have been also updated. A number of newly identified modified ribonucleosides and more than one hundred functionally and structurally characterized proteins from various organisms have been added. In the RNA sequences section, snRNAs and snoRNAs with experimentally mapped modified nucleosides have been added and the current collection of rRNA and tRNA sequences has been substantially enlarged. To facilitate literature searches, each record in MODOMICS has been cross-referenced to other databases and to selected key publications. New options for database searching and querying have been implemented, including a BLAST search of protein sequences and a PARALIGN search of the collected nucleic acid sequences.
TL;DR: A major increase in the number of tRNA predictions and genomes analyzed is described, but more importantly, the integration of new analytic and functional data to improve the quality and biological context of t RNA gene predictions are described.
Abstract: Transfer RNAs represent the largest, most ubiquitous class of non-protein coding RNA genes found in all living organisms. The tRNAscan-SE search tool has become the de facto standard for annotating tRNA genes in genomes, and the Genomic tRNA Database (GtRNAdb) was created as a portal for interactive exploration of these gene predictions. Since its published description in 2009, the GtRNAdb has steadily grown in content, and remains the most commonly cited web-based source of tRNA gene information. In this update, we describe not only a major increase in the number of tRNA predictions (>367000) and genomes analyzed (>4370), but more importantly, the integration of new analytic and functional data to improve the quality and biological context of tRNA gene predictions. New information drawn from other sources includes tRNA modification data, epigenetic data, single nucleotide polymorphisms, gene expression and evolutionary conservation. A richer set of analytic data is also presented, including better tRNA functional prediction, non-canonical features, predicted structural impacts from sequence variants and minimum free energy structural predictions. Views of tRNA genes in genomic context are provided via direct links to the UCSC genome browsers. The database can be searched by sequence or gene features, and is available at http://gtrnadb.ucsc.edu/.
TL;DR: This review highlights new findings on the diverse pathways of tRNA maturation, and on the formation and function of a number of modifications, on the regulation of t RNA biosynthesis, quality control tRNA turnover mechanisms, widespread tRNA cleavage pathways activated in response to stress and other growth conditions.
Abstract: tRNA biology has come of age, revealing an unprecedented level of understanding and many unexpected discoveries along the way. This review highlights new findings on the diverse pathways of tRNA maturation, and on the formation and function of a number of modifications. Topics of special focus include the regulation of tRNA biosynthesis, quality control tRNA turnover mechanisms, widespread tRNA cleavage pathways activated in response to stress and other growth conditions, emerging evidence of signaling pathways involving tRNA and cleavage fragments, and the sophisticated intracellular tRNA trafficking that occurs during and after biosynthesis.
TL;DR: Historical Perspective on RNA-Nucleoside Modifications RNA-Modifying and RNA-Editing Enzymes Detection and Structure Analysis of Modified Nucleosides in RNA by Mass Spectrometry Incorporation of modified N nucleosides or Nucleotide in RNA (Nuclear Magnetic Resonance Studies).
Abstract: Historical Perspective on RNA-Nucleoside Modifications RNA-Modifying and RNA-Editing Enzymes Detection and Structure Analysis of Modified Nucleosides in RNA by Mass Spectrometry Incorporation of Modified Nucleosides or Nucleotides in RNA (Nuclear Magnetic Resonance Studies) Biophysical and Conformational Properties of Modified Nucleosides in RNA Effects of Pseudouridylation on tRNA Hydration and Dynamics Modulation Role of Modified Nucleotides in Anticodon-Anticodon Interaction Mechanisms of RNA-Modifying and Editing Enzymes Structural Basis of Base Exchange by tRNA-Guanine Transglycosylases Biosynthesis and Functions of Modified Neuclosides in Eurkaryotic mRNA Posttranscriptional Modifications in the U Small Nuclear RNAs The Pseudouridine Residues of rRNA Small Nucleolar RNAs Guide the Ribose Methylations of Eukaryotic rRNAs Functional Aspects of the Three Modified Nucleotides in Yeast Mitochondrial Large-Subunit rRNA Regulatory Aspects of rRNA Modifications and Pre-rRNA Processing Editing by tRNA RNA Editing by Base Conversion in Plant Organellar RNAs Apolipoprotein B mRNA Editing Adenosine-to-Inosine Conversion in mRNA Nucleoside Deaminases for Cytidine and Adenosine Mitochondrial mRNA Editing in Kinetoplastid Protozoa RNA Editing in Physarum Mitochondria Cotranscriptional Paramyxovirus mRNA Editing Intracellular Locations of RNA-Modifying Enzymes Genetics and Regulation of Base Modification in the tRNA and rRNA of Prokaryotes and Eukaryotes Links Between tRNA Modification and Metabolism and Modified Nucleosides as Tumor Markers Modified Nucleosides in Translation Importance of Modified Nucleotides in Replication of Retroviruses, Plant Pararetroviruses and Retrotransposons Modified Nucleotides Always Were