A-to-I RNA editing is the most common non-transient epitranscriptome modification. It plays several roles in human physiology and has been linked to several disorders. Large-scale deep transcriptome sequencing has fostered the characterization of A-to-I editing at the single nucleotide level and the development of dedicated computational resources.
View Article and Find Full Text PDFThe Rfam database, a widely used repository of non-coding RNA families, has undergone significant updates in release 15.0. This paper introduces major improvements, including the expansion of Rfamseq to 26 106 genomes, a 76% increase, incorporating the latest UniProt reference proteomes and additional viral genomes.
View Article and Find Full Text PDFThe Rfam database, a widely-used repository of non-coding RNA (ncRNA) families, has undergone significant updates in release 15.0. This paper introduces major improvements, including the expansion of Rfamseq to 26,106 genomes, a 76% increase, incorporating the latest UniProt reference proteomes and additional viral genomes.
View Article and Find Full Text PDFHepatitis C virus (HCV) is a plus-stranded RNA virus that often chronically infects liver hepatocytes and causes liver cirrhosis and cancer. These viruses replicate their genomes employing error-prone replicases. Thereby, they routinely generate a large 'cloud' of RNA genomes (quasispecies) which-by trial and error-comprehensively explore the sequence space available for functional RNA genomes that maintain the ability for efficient replication and immune escape.
View Article and Find Full Text PDFThe protein structure prediction problem has been solved for many types of proteins by AlphaFold. Recently, there has been considerable excitement to build off the success of AlphaFold and predict the 3D structures of RNAs. RNA prediction methods use a variety of techniques, from physics-based to machine learning approaches.
View Article and Find Full Text PDFSequence variation in a widespread, recurrent, structured RNA 3D motif, the Sarcin/Ricin (S/R), was studied to address three related questions: First, how do the stabilities of structured RNA 3D motifs, composed of non-Watson-Crick (non-WC) basepairs, compare to WC-paired helices of similar length and sequence? Second, what are the effects on the stabilities of such motifs of isosteric and non-isosteric base substitutions in the non-WC pairs? And third, is there selection for particular base combinations in non-WC basepairs, depending on the temperature regime to which an organism adapts? A survey of large and small subunit rRNAs from organisms adapted to different temperatures revealed the presence of systematic sequence variations at many non-WC paired sites of S/R motifs. UV melting analysis and enzymatic digestion assays of oligonucleotides containing the motif suggest that more stable motifs tend to be more rigid. We further found that the base substitutions at non-Watson-Crick pairing sites can significantly affect the thermodynamic stabilities of S/R motifs and these effects are highly context specific indicating the importance of base-stacking and base-phosphate interactions on motif stability.
View Article and Find Full Text PDFNon-coding RNAs (ncRNA) are essential for all life, and their functions often depend on their secondary (2D) and tertiary structure. Despite the abundance of software for the visualisation of ncRNAs, few automatically generate consistent and recognisable 2D layouts, which makes it challenging for users to construct, compare and analyse structures. Here, we present R2DT, a method for predicting and visualising a wide range of RNA structures in standardised layouts.
View Article and Find Full Text PDFNon-coding RNAs are essential for all life and carry out a wide range of functions. Information about these molecules is distributed across dozens of specialized resources. RNAcentral is a database of non-coding RNA sequences that provides a unified access point to non-coding RNA annotations from >40 member databases and helps provide insight into the function of these RNAs.
View Article and Find Full Text PDFMany non-coding RNAs have been identified and may function by forming 2D and 3D structures. RNA hairpin and internal loops are often represented as unstructured on secondary structure diagrams, but RNA 3D structures show that most such loops are structured by non-Watson-Crick basepairs and base stacking. Moreover, different RNA sequences can form the same RNA 3D motif.
View Article and Find Full Text PDFRNA 3D motifs occupy places in structured RNA molecules that correspond to the hairpin, internal and multi-helix junction "loops" of their secondary structure representations. As many as 40% of the nucleotides of an RNA molecule can belong to these structural elements, which are distinct from the regular double helical regions formed by contiguous AU, GC, and GU Watson-Crick basepairs. With the large number of atomic- or near atomic-resolution 3D structures appearing in a steady stream in the PDB/NDB structure databases, the automated identification, extraction, comparison, clustering and visualization of these structural elements presents an opportunity to enhance RNA science.
View Article and Find Full Text PDFPredicting RNA 3D structure from sequence is a major challenge in biophysics. An important sub-goal is accurately identifying recurrent 3D motifs from RNA internal and hairpin loop sequences extracted from secondary structure (2D) diagrams. We have developed and validated new probabilistic models for 3D motif sequences based on hybrid Stochastic Context-Free Grammars and Markov Random Fields (SCFG/MRF).
View Article and Find Full Text PDFThe RNA 3D Structure-to-Multiple Sequence Alignment Server (R3D-2-MSA) is a new web service that seamlessly links RNA three-dimensional (3D) structures to high-quality RNA multiple sequence alignments (MSAs) from diverse biological sources. In this first release, R3D-2-MSA provides manual and programmatic access to curated, representative ribosomal RNA sequence alignments from bacterial, archaeal, eukaryal and organellar ribosomes, using nucleotide numbers from representative atomic-resolution 3D structures. A web-based front end is available for manual entry and an Application Program Interface for programmatic access.
View Article and Find Full Text PDFRNA secondary structure diagrams familiar to molecular biologists summarize at a glance the folding of RNA chains to form Watson–Crick paired double helices. However, they can be misleading: First of all, they imply that the nucleotides in loops and linker segments, which can amount to 35% to 50% of a structured RNA, do not significantly interact with other nucleotides. Secondly, they give the impression that RNA molecules are loosely organized in three-dimensional (3D) space.
View Article and Find Full Text PDFThe Nucleic Acid Database (NDB) (http://ndbserver.rutgers.edu) is a web portal providing access to information about 3D nucleic acid structures and their complexes.
View Article and Find Full Text PDFNanomedicine (Lond)
July 2013
The second International Conference on RNA Nanotechnology and Therapeutics was held on the 3-5 April in Lexington, (KY, USA). The focus of the conference was on leveraging the unique chemical and biological properties of RNA to promote transformative advances in medicine. The conference convened more than 200 researchers from 15 countries and many disciplines, roughly double the participants of the first conference.
View Article and Find Full Text PDF5-Fluoroanthranilic acid (FAA)-resistant mutants were selected in homothallic diploids of three Saccharomyces species, taking care to isolate mutants of independent origin. Mutations were assigned to complementation groups by interspecific complementation with S. cerevisiae tester strains.
View Article and Find Full Text PDFWe use discrete event stochastic simulations to characterize the parameter space of a model of icosahedral viral capsid assembly as functions of monomer-monomer binding rates. The simulations reveal a parameter space characterized by three major assembly mechanisms, a standard nucleation-limited monomer-accretion pathway and two distinct hierarchical assembly pathways, as well as unproductive regions characterized by kinetically trapped species. Much of the productive parameter space also consists of border regions between these domains where hybrid pathways are likely to operate.
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