Computational approaches for alternative and transient secondary structures of ribonucleic acids

2018 ◽  
Vol 18 (3) ◽  
pp. 182-191
Author(s):  
Tsukasa Fukunaga ◽  
Michiaki Hamada
Keyword(s):  
Secondary Structures ◽  
Living Cells ◽  
Translation Regulation ◽  
Folding Pathway ◽  
Rna Structures ◽  
Computational Approaches ◽  
Rna Secondary Structures ◽  
Ribonucleic Acids ◽  
Alternative Structures ◽  
Regulatory Processes

Abstract Transient and alternative structures of ribonucleic acids (RNAs) play essential roles in various regulatory processes, such as translation regulation in living cells. Because experimental analyses for RNA structures are difficult and time-consuming, computational approaches based on RNA secondary structures are promising. In this article, we review computational methods for detecting and analyzing transient/alternative secondary structures of RNAs, including static approaches based on probabilistic distributions of RNA secondary structures and dynamic approaches such as kinetic folding and folding pathway predictions.

scholarly journals Characteristics and Prediction of RNA Structure

2014 ◽  
Vol 2014 ◽  
pp. 1-10
Author(s):  
Hengwu Li ◽  
Daming Zhu ◽  
Caiming Zhang ◽  
Huijian Han ◽  
Keith A. Crandall
Keyword(s):  
Rna Structure ◽  
Structure Prediction ◽  
Rna Folding ◽  
Golden Section ◽  
Hierarchical Structures ◽  
Secondary Structures ◽  
Sequence Length ◽  
Rna Structures ◽  
Rna Secondary Structures ◽  
Hierarchical Folding

RNA secondary structures with pseudoknots are often predicted by minimizing free energy, which is NP-hard. Most RNAs fold during transcription from DNA into RNA through a hierarchical pathway wherein secondary structures form prior to tertiary structures. Real RNA secondary structures often have local instead of global optimization because of kinetic reasons. The performance of RNA structure prediction may be improved by considering dynamic and hierarchical folding mechanisms. This study is a novel report on RNA folding that accords with the golden mean characteristic based on the statistical analysis of the real RNA secondary structures of all 480 sequences from RNA STRAND, which are validated by NMR or X-ray. The length ratios of domains in these sequences are approximately 0.382L, 0.5L, 0.618L, andL, whereLis the sequence length. These points are just the important golden sections of sequence. With this characteristic, an algorithm is designed to predict RNA hierarchical structures and simulate RNA folding by dynamically folding RNA structures according to the above golden section points. The sensitivity and number of predicted pseudoknots of our algorithm are better than those of the Mfold, HotKnots, McQfold, ProbKnot, and Lhw-Zhu algorithms. Experimental results reflect the folding rules of RNA from a new angle that is close to natural folding.

scholarly journals RAG: RNA-As-Graphs database—concepts, analysis, and features

1987 ◽  
Vol 5 (1-2) ◽  
pp. 1285-1291 ◽  
Author(s):  
Hin Hark Gan ◽  
Daniela Fera ◽  
Julie Zorn ◽  
Nahum Shiffeldrim ◽  
Michael Tang ◽  
...  
Keyword(s):  
Structural Diversity ◽  
Secondary Structures ◽  
Sequence Length ◽  
Structural Elements ◽  
Rna Structures ◽  
Rna Motifs ◽  
Rna Secondary Structures ◽  
Vertex Number ◽  
Dual Graphs ◽  
Tree Graphs

Motivation Understanding RNA's structural diversity is vital for identifying novel RNA structures and pursuing RNA genomics initiatives. By classifying RNA secondary motifs based on correlations between conserved RNA secondary structures and functional properties, we offer an avenue for predicting novel motifs. Although several RNA databases exist, no comprehensive schemes are available for cataloguing the range and diversity of RNA's structural repertoire. Results Our RNA-As-Graphs (RAG) database describes and ranks all mathematically possible (including existing and candidate) RNA secondary motifs on the basis of graphical enumeration techniques. We represent RNA secondary structures as two-dimensional graphs (networks), specifying the connectivity between RNA secondary structural elements, such as loops, bulges, stems and junctions. We archive RNA tree motifs as ‘tree graphs’ and other RNAs, including pseudoknots, as general ‘dual graphs’. All RNA motifs are catalogued by graph vertex number (a measure of sequence length) and ranked by topological complexity. The RAG inventory immediately suggests candidates for novel RNA motifs, either naturally occurring or synthetic, and thereby might stimulate the prediction and design of novel RNA motifs. Availability The database is accessible on the web at http://monod.biomath.nyu.edu/rna Contact [email protected]

scholarly journals Computational Discovery of Evolutionary Conserved Enterovirus 71 RNA Secondary Structures

2018 ◽  
Author(s):  
Nathan Fridlyand ◽  
Alexander N Lukashev ◽  
Andrey Chursov ◽  
Franco M Venanzi ◽  
Jonathan W Yewdell ◽  
...  
Keyword(s):  
Rna Structure ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Enterovirus 71 ◽  
Secondary Structures ◽  
Rna Structures ◽  
Alternative Structures ◽  
Evolutionarily Conserved ◽  
Computational Discovery ◽  
Rna Switch

Viral RNAs store information in their sequence and structure. Little, however is known about the contribution of RNA structure to viral replication and evolution. We previously described RNA ISRAEU to computationally identify structured regions in viral RNA based on evolutionary conservation of predicted structures. Here, we apply RNA GUESS (Generator of Uniformly Evolved Secondary Structures) to better understand enterovirus 71, a highly pathogenic human picornavirus. RNA GUESS identified previously known evolutionarily conserved picornavirus RNA structures, and uniquely predicted RNA structures with significant structural conservation despite the lack of an obvious sequence conservation. One structure consists of a stretch of obligatorily unpaired nucleotides that can potentially interact with RNA-binding proteins and siRNAs. Another, forms a potential RNA switch that can form two alternative structures while the third and fourth constitute hairpin-like structures. These findings provide a launching point for physical and genetic studies regarding the function and structures of these RNA elements.

scholarly journals In Vivo and In Vitro Genome-Wide Profiling of RNA Secondary Structures Reveals Key Regulatory Features in Plasmodium falciparum

2021 ◽  
Vol 11 ◽  
Author(s):  
Yanwei Qi ◽  
Yuhong Zhang ◽  
Guixing Zheng ◽  
Bingxia Chen ◽  
Mengxin Zhang ◽  
...  
Keyword(s):  
Secondary Structure ◽  
Rna Structure ◽  
Rna Secondary Structure ◽  
Secondary Structures ◽  
Rna Structures ◽  
Trophozoite Stage ◽  
Rna Secondary Structures ◽  
Biological Programme

It is widely accepted that the structure of RNA plays important roles in a number of biological processes, such as polyadenylation, splicing, and catalytic functions. Dynamic changes in RNA structure are able to regulate the gene expression programme and can be used as a highly specific and subtle mechanism for governing cellular processes. However, the nature of most RNA secondary structures in Plasmodium falciparum has not been determined. To investigate the genome-wide RNA secondary structural features at single-nucleotide resolution in P. falciparum, we applied a novel high-throughput method utilizing the chemical modification of RNA structures to characterize these structures. Structural data from parasites are in close agreement with the known 18S ribosomal RNA secondary structures of P. falciparum and can help to predict the in vivo RNA secondary structure of a total of 3,396 transcripts in the ring-stage and trophozoite-stage developmental cycles. By parallel analysis of RNA structures in vivo and in vitro during the Plasmodium parasite ring-stage and trophozoite-stage intraerythrocytic developmental cycles, we identified some key regulatory features. Recent studies have established that the RNA structure is a ubiquitous and fundamental regulator of gene expression. Our study indicate that there is a critical connection between RNA secondary structure and mRNA abundance during the complex biological programme of P. falciparum. This work presents a useful framework and important results, which may facilitate further research investigating the interactions between RNA secondary structure and the complex biological programme in P. falciparum. The RNA secondary structure characterized in this study has potential applications and important implications regarding the identification of RNA structural elements, which are important for parasite infection and elucidating host-parasite interactions and parasites in the environment.

scholarly journals Comparative analysis of coronavirus genomic RNA structure reveals conservation in SARS-like coronaviruses

2020 ◽  
Author(s):  
Wes Sanders ◽  
Ethan J. Fritch ◽  
Emily A. Madden ◽  
Rachel L. Graham ◽  
Heather A. Vincent ◽  
...  
Keyword(s):  
Secondary Structure ◽  
Rna Structure ◽  
Rna Secondary Structure ◽  
Molecular Mechanisms ◽  
Selective Pressure ◽  
Secondary Structures ◽  
Rna Structures ◽  
Rna Secondary Structures ◽  
The Past ◽  
Novel Strategy

AbstractCoronaviruses, including SARS-CoV-2 the etiological agent of COVID-19 disease, have caused multiple epidemic and pandemic outbreaks in the past 20 years1–3. With no vaccines, and only recently developed antiviral therapeutics, we are ill equipped to handle coronavirus outbreaks4. A better understanding of the molecular mechanisms that regulate coronavirus replication and pathogenesis is needed to guide the development of new antiviral therapeutics and vaccines. RNA secondary structures play critical roles in multiple aspects of coronavirus replication, but the extent and conservation of RNA secondary structure across coronavirus genomes is unknown5. Here, we define highly structured RNA regions throughout the MERS-CoV, SARS-CoV, and SARS-CoV-2 genomes. We find that highly stable RNA structures are pervasive throughout coronavirus genomes, and are conserved between the SARS-like CoV. Our data suggests that selective pressure helps preserve RNA secondary structure in coronavirus genomes, suggesting that these structures may play important roles in virus replication and pathogenesis. Thus, disruption of conserved RNA secondary structures could be a novel strategy for the generation of attenuated SARS-CoV-2 vaccines for use against the current COVID-19 pandemic.

scholarly journals Using SHAPE-MaP To Model RNA Secondary Structure and Identify 3′UTR Variation in Chikungunya Virus

2020 ◽  
Vol 94 (24) ◽  
Author(s):  
Emily A. Madden ◽  
Kenneth S. Plante ◽  
Clayton R. Morrison ◽  
Katrina M. Kutchko ◽  
Wes Sanders ◽  
...  
Keyword(s):  
Secondary Structure ◽  
Virus Replication ◽  
Rna Structure ◽  
Rna Secondary Structure ◽  
Chikungunya Virus ◽  
Secondary Structures ◽  
Rna Structures ◽  
Functional Importance ◽  
Rna Secondary Structures ◽  
Mosquito Cells

ABSTRACT Chikungunya virus (CHIKV) is a mosquito-borne alphavirus associated with debilitating arthralgia in humans. RNA secondary structure in the viral genome plays an important role in the lifecycle of alphaviruses; however, the specific role of RNA structure in regulating CHIKV replication is poorly understood. Our previous studies found little conservation in RNA secondary structure between alphaviruses, and this structural divergence creates unique functional structures in specific alphavirus genomes. Therefore, to understand the impact of RNA structure on CHIKV biology, we used SHAPE-MaP to inform the modeling of RNA secondary structure throughout the genome of a CHIKV isolate from the 2013 Caribbean outbreak. We then analyzed regions of the genome with high levels of structural specificity to identify potentially functional RNA secondary structures and identified 23 regions within the CHIKV genome with higher than average structural stability, including four previously identified, functionally important CHIKV RNA structures. We also analyzed the RNA flexibility and secondary structures of multiple 3′UTR variants of CHIKV that are known to affect virus replication in mosquito cells. This analysis found several novel RNA structures within these 3′UTR variants. A duplication in the 3′UTR that enhances viral replication in mosquito cells led to an overall increase in the amount of unstructured RNA in the 3′UTR. This analysis demonstrates that the CHIKV genome contains a number of unique, specific RNA secondary structures and provides a strategy for testing these secondary structures for functional importance in CHIKV replication and pathogenesis. IMPORTANCE Chikungunya virus (CHIKV) is a mosquito-borne RNA virus that causes febrile illness and debilitating arthralgia in humans. CHIKV causes explosive outbreaks but there are no approved therapies to treat or prevent CHIKV infection. The CHIKV genome contains functional RNA secondary structures that are essential for proper virus replication. Since RNA secondary structures have only been defined for a small portion of the CHIKV genome, we used a chemical probing method to define the RNA secondary structures of CHIKV genomic RNA. We identified 23 highly specific structured regions of the genome, and confirmed the functional importance of one structure using mutagenesis. Furthermore, we defined the RNA secondary structure of three CHIKV 3′UTR variants that differ in their ability to replicate in mosquito cells. Our study highlights the complexity of the CHIKV genome and describes new systems for designing compensatory mutations to test the functional relevance of viral RNA secondary structures.

Mapping circular RNA structures in living cells by SHAPE-MaP

Methods ◽  
2021 ◽  
Author(s):  
Si-Kun Guo ◽  
Fang Nan ◽  
Chu-Xiao Liu ◽  
Li Yang ◽  
Ling-Ling Chen
Keyword(s):  
Circular Rna ◽  
Living Cells ◽  
Rna Structures

scholarly journals Mutually exclusive RNA secondary structures regulate translation initiation of DinQ in Escherichia coli

RNA ◽  
2016 ◽  
Vol 22 (11) ◽  
pp. 1739-1749 ◽  
Author(s):  
Knut I. Kristiansen ◽  
Ragnhild Weel-Sneve ◽  
James A. Booth ◽  
Magnar Bjørås
Keyword(s):  
Escherichia Coli ◽  
Translation Initiation ◽  
Secondary Structures ◽  
Rna Secondary Structures

Interval-Based Similarity for Classifying Conserved RNA Secondary Structures

2016 ◽  
Vol 31 (3) ◽  
pp. 78-85 ◽  
Author(s):  
Qingfeng Chen ◽  
Yi-Ping Phoebe Chen ◽  
Chengqi Zhang
Keyword(s):  
Secondary Structures ◽  
Rna Secondary Structures
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