RNA Structure Analysis: A Multifaceted Approach

1999 ◽  
Author(s):  
Bruce A. Shapiro ◽  
Wojciech Kasprzak
Keyword(s):  
Nucleic Acid ◽  
Secondary Structure ◽  
Tertiary Structure ◽  
Hammerhead Ribozyme ◽  
3D Structure ◽  
Computer Prediction ◽  
Rna Molecules ◽  
Tertiary Interactions ◽  
The One ◽  
Secondary And Tertiary Structure

Genomic information (nucleic acid and amino acid sequences) completely determines the characteristics of the nucleic acid and protein molecules that express a living organism’s function. One of the greatest challenges in which computation is playing a role is the prediction of higher order structure from the one-dimensional sequence of genes. Rules for determining macromolecule folding have been continually evolving. Specifically in the case of RNA (ribonucleic acid) there are rules and computer algorithms/systems (see below) that partially predict and can help analyze the secondary and tertiary interactions of distant parts of the polymer chain. These successes are very important for determining the structural and functional characteristics of RNA in disease processes and hi the cell life cycle. It has been shown that molecules with the same function have the potential to fold into similar structures though they might differ in their primary sequences. This fact also illustrates the importance of secondary and tertiary structure in relation to function. Examples of such constancy in secondary structure exist in transfer RNAs (tRNAs), 5s RNAs, 16s RNAs, viroid RNAs, and portions of retroviruses such as HIV. The secondary and tertiary structure of tRNA Phe (Kim et al., 1974), of a hammerhead ribozyme (Pley et al., 1994), and of Tetrahymena (Cate et al., 1996a, 1996b) have been shown by their crystal structure. Currently little is known of tertiary interactions, but studies on tRNA indicate these are weaker than secondary structure interactions (Riesner and Romer, 1973; Crothers and Cole, 1978; Jaeger et al., 1989b). It is very difficult to crystallize and/or get nuclear magnetic resonance spectrum data for large RNA molecules. Therefore, a logical place to start in determining the 3D structure of RNA is computer prediction of the secondary structure. The sequence (primary structure) of an RNA molecule is relatively easy to produce. Because experimental methods for determining RNA secondary and tertiary structure (when the primary sequence folds back on itself and forms base pairs) have not kept pace with the rapid discovery of RNA molecules and their function, use of and methods for computer prediction of secondary and tertiary structures have increasingly been developed.

scholarly journals Viroids: unusual small pathogenic RNAs.

2004 ◽  
Vol 51 (3) ◽  
pp. 587-607 ◽  
Author(s):  
Anna Góra-Sochacka
Keyword(s):  
Secondary Structure ◽  
Hammerhead Ribozyme ◽  
Direct Interaction ◽  
Plant Diseases ◽  
Plant Host ◽  
Rolling Circle ◽  
Rna Molecules ◽  
Viroid Replication ◽  
Plant Genes ◽  
Rolling Circle Mechanism

Viroids are small (about 300 nucleotides), single-stranded, circular, non-encapsidated pathogenic RNA molecules. They do not code for proteins and thus depend on plant host enzymes for their replication and other functions. They induce plant diseases by direct interaction with host factors but the mechanism of pathogenicity is still unknown. They can alter the expression of selected plant genes important for growth and development. Viroids belong to two families, the Avsunviroidae and the Pospiviroidae. Viroids of the Avsunviroidae family adopt a branched or quasi rod-like secondary structure in their native state. Members of the Pospiviroidae family adopt a rod-like secondary structure. In such native structures five structural/functional domains have been identified: central (C), pathogenicity, variable and two terminal domains. The central conserved region (CCR) within the C domain characterizes viroids of the Pospiviroidae. Specific secondary structures of this region play an important role in viroid replication and processing. Viroids of the Avsunviroidae family lack a CCR but possess self-cleaving properties by forming hammerhead ribozyme structures; they accumulate and replicate in chloroplasts, whereas members of the Pospiviroidae family have a nuclear localization. Viroid replication occurs via a rolling circle mechanism using either a symmetric or asymmetric pathway in three steps, RNA transcription, processing and ligation.

Unfolding Single RNA Molecules with Optical Tweezers

2001 ◽  
Vol 7 (S2) ◽  
pp. 26-27
Author(s):  
Carlos Bustamante ◽  
Jan Liphardt ◽  
Bibiana Onoa ◽  
Steven B. Smith ◽  
Delphine Collin ◽  
...  
Keyword(s):  
Secondary Structure ◽  
Optical Tweezers ◽  
Single Molecule ◽  
Structure Prediction ◽  
Secondary Structure Prediction ◽  
Structural Features ◽  
Rna Molecules ◽  
Group I ◽  
Tertiary Folding ◽  
Tertiary Interactions

RNA molecules must fold into specific three-dimensional shapes to perform their structural and catalytic functions. Unlike proteins, RNAs secondary structural features are usually stable enough to form by themselves in solution. The reason is that in RNA, the stabilization energy gained from the formation of secondary structure is substantially larger than the energies involved in tertiary interactions. As a result, the formation of tertiary interactions is expected to alter only slightly the pre-existing secondary structural contacts. Moreover, secondary structure prediction is robust and can be made without taking into consideration tertiary folding. However, bulk studies of the energetics and kinetics of their secondary and tertiary folding are often frustrated by the presence of multiple species and multiple folding pathways in solution. These problems are circumvented in single-molecule studies in which the folding/unfolding trajectories of the individual molecules can be followed. The T. thermophila group I intron ribozyme is organized into several domains whose mechanical unfolding can be investigated independently, and whose tertiary contacts are stabilized by numerous Mg++ ions.We have begun characterization of the ribozyme by analysis of the P5abc domain because:

scholarly journals 3D based on 2D: Calculating helix angles and stacking patterns using forgi 2.0, an RNA Python library centered on secondary structure elements.

F1000Research ◽  
2019 ◽  
Vol 8 ◽  
pp. 287 ◽  
Author(s):  
Bernhard C. Thiel ◽  
Irene K. Beckmann ◽  
Peter Kerpedjiev ◽  
Ivo L. Hofacker
Keyword(s):  
Secondary Structure ◽  
Rna Secondary Structure ◽  
Tertiary Structure ◽  
3D Structure ◽  
Coarse Grained ◽  
Helix Axis ◽  
Structure Representation ◽  
File Formats ◽  
3D Information ◽  
Stacking Patterns

We present forgi, a Python library to analyze the tertiary structure of RNA secondary structure elements. Our representation of an RNA molecule is centered on secondary structure elements (stems, bulges and loops). By fitting a cylinder to the helix axis, these elements are carried over into a coarse-grained 3D structure representation. Integration with Biopython allows for handling of all-atom 3D information. forgi can deal with a variety of file formats including dotbracket strings, PDB and MMCIF files. We can handle modified residues, missing residues, cofold and multifold structures as well as nucleotide numbers starting at arbitrary positions. We apply this library to the study of stacking helices in junctions and pseudoknots and investigate how far stacking helices in solved experimental structures can divert from coaxial geometries.

A deep attention network for predicting amino acid signals in the formation of α-helices

2020 ◽  
Vol 18 (05) ◽  
pp. 2050028
Author(s):  
A. Visibelli ◽  
P. Bongini ◽  
A. Rossi ◽  
N. Niccolai ◽  
M. Bianchini
Keyword(s):  
Secondary Structure ◽  
Tertiary Structure ◽  
Protein Structures ◽  
Attention Mechanism ◽  
Primary Role ◽  
Large Dataset ◽  
Secondary Structure Formation ◽  
The Past ◽  
Secondary And Tertiary Structure ◽  
Machine Learning Models

The secondary and tertiary structure of a protein has a primary role in determining its function. Even though many folding prediction algorithms have been developed in the past decades — mainly based on the assumption that folding instructions are encoded within the protein sequence — experimental techniques remain the most reliable to establish protein structures. In this paper, we searched for signals related to the formation of [Formula: see text]-helices. We carried out a statistical analysis on a large dataset of experimentally characterized secondary structure elements to find over- or under-occurrences of specific amino acids defining the boundaries of helical moieties. To validate our hypothesis, we trained various Machine Learning models, each equipped with an attention mechanism, to predict the occurrence of [Formula: see text]-helices. The attention mechanism allows to interpret the model’s decision, weighing the importance the predictor gives to each part of the input. The experimental results show that different models focus on the same subsequences, which can be seen as codes driving the secondary structure formation.

Synthetic bPNAs as Allosteric Triggers of Hammerhead Ribozyme Catalysis

2019 ◽  
Author(s):  
Dennis Bong ◽  
Yufeng Liang ◽  
Jie Mao
Keyword(s):  
Nucleic Acid ◽  
Secondary Structure ◽  
Structure Function ◽  
Structural Biology ◽  
Peptide Nucleic Acid ◽  
Hammerhead Ribozyme ◽  
Structural Elements ◽  
Sugar Phosphate ◽  
Turn On ◽  
Bond Scission

The biochemistry and structural biology of the hammerhead ribozyme (HHR) has been well-elucidated. The secondary and tertiary structural elements that enable sugar-phosphate bond scission to be be catalyzed by this RNA are clearly understood. We have taken advantage of this knowledge base to test the extent to which synthetic molecules, may be used to trigger structure in secondary structure and tertiary interactions and thereby control HHR catalysis. These molecules belong to a family of molecules we call generally call “bPNAs” based on our work on bifacial peptide nucleic acid (bPNA). This family of molecules display the “bifacial” heterocycle melamine, which acts as a base-triple upon capturing two equivalents of thymine or uracil. Loosely structured internal oligouridylate bulges of 4-20 nucleotides can be restructured as triplex hybrid stems upon binding bPNAs. As such, a duplex stem element can be replaced with a bPNA triplex hybrid stem; similarly, a tertiary loop-stem interaction can be replaced with a loop-bPNA-stem complex. In this chapter, we discuss how bPNAs are prepared and applied to study structure-function turn-on in the hammerhead ribozyme system.

Synthetic bPNAs as Allosteric Triggers of Hammerhead Ribozyme Catalysis

2019 ◽  
Author(s):  
Dennis Bong ◽  
Yufeng Liang ◽  
Jie Mao
Keyword(s):  
Nucleic Acid ◽  
Secondary Structure ◽  
Structure Function ◽  
Structural Biology ◽  
Peptide Nucleic Acid ◽  
Hammerhead Ribozyme ◽  
Structural Elements ◽  
Sugar Phosphate ◽  
Turn On ◽  
Bond Scission

The biochemistry and structural biology of the hammerhead ribozyme (HHR) has been well-elucidated. The secondary and tertiary structural elements that enable sugar-phosphate bond scission to be be catalyzed by this RNA are clearly understood. We have taken advantage of this knowledge base to test the extent to which synthetic molecules, may be used to trigger structure in secondary structure and tertiary interactions and thereby control HHR catalysis. These molecules belong to a family of molecules we call generally call “bPNAs” based on our work on bifacial peptide nucleic acid (bPNA). This family of molecules display the “bifacial” heterocycle melamine, which acts as a base-triple upon capturing two equivalents of thymine or uracil. Loosely structured internal oligouridylate bulges of 4-20 nucleotides can be restructured as triplex hybrid stems upon binding bPNAs. As such, a duplex stem element can be replaced with a bPNA triplex hybrid stem; similarly, a tertiary loop-stem interaction can be replaced with a loop-bPNA-stem complex. In this chapter, we discuss how bPNAs are prepared and applied to study structure-function turn-on in the hammerhead ribozyme system.

scholarly journals 3D based on 2D: Calculating helix angles and stacking patterns using forgi 2.0, an RNA Python library centered on secondary structure elements.

F1000Research ◽  
2019 ◽  
Vol 8 ◽  
pp. 287
Author(s):  
Bernhard C. Thiel ◽  
Irene K. Beckmann ◽  
Peter Kerpedjiev ◽  
Ivo L. Hofacker
Keyword(s):  
Secondary Structure ◽  
Rna Secondary Structure ◽  
Tertiary Structure ◽  
3D Structure ◽  
Coarse Grained ◽  
Helix Axis ◽  
Structure Representation ◽  
File Formats ◽  
3D Information ◽  
Stacking Patterns

We present forgi, a Python library to analyze the tertiary structure of RNA secondary structure elements. Our representation of an RNA molecule is centered on secondary structure elements (stems, bulges and loops). By fitting a cylinder to the helix axis, these elements are carried over into a coarse-grained 3D structure representation. Integration with Biopython allows for handling of all-atom 3D information. forgi can deal with a variety of file formats including dotbracket strings, PDB and MMCIF files. We can handle modified residues, missing residues, cofold and multifold structures as well as nucleotide numbers starting at arbitrary positions. We apply this library to the study of stacking helices in junctions and pseudo knots and investigate how far stacking helices in solved experimental structures can divert from coaxial geometries.

scholarly journals Structural 3D Domain Reconstruction of the RNA Genome from Viruses with Secondary Structure Models

Viruses ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1555
Author(s):  
Simón Poblete ◽  
Horacio V. Guzman
Keyword(s):  
Secondary Structure ◽  
High Reliability ◽  
3D Structure ◽  
Three Dimensional ◽  
Coarse Grained ◽  
Entire Genome ◽  
Rna Molecules ◽  
Secondary Structure Models ◽  
Rna Genome ◽  
Self Association

Three-dimensional RNA domain reconstruction is important for the assembly, disassembly and delivery functionalities of a packed proteinaceus capsid. However, to date, the self-association of RNA molecules is still an open problem. Recent chemical probing reports provide, with high reliability, the secondary structure of diverse RNA ensembles, such as those of viral genomes. Here, we present a method for reconstructing the complete 3D structure of RNA genomes, which combines a coarse-grained model with a subdomain composition scheme to obtain the entire genome inside proteinaceus capsids based on secondary structures from experimental techniques. Despite the amount of sampling involved in the folded and also unfolded RNA molecules, advanced microscope techniques can provide points of anchoring, which enhance our model to include interactions between capsid pentamers and RNA subdomains. To test our method, we tackle the satellite tobacco mosaic virus (STMV) genome, which has been widely studied by both experimental and computational communities. We provide not only a methodology to structurally analyze the tertiary conformations of the RNA genome inside capsids, but a flexible platform that allows the easy implementation of features/descriptors coming from both theoretical and experimental approaches.

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