scholarly journals Current perspectives on RNA secondary structure probing

2014 ◽  
Vol 42 (4) ◽  
pp. 1251-1255 ◽  
Author(s):  
Julia Kenyon ◽  
Liam Prestwood ◽  
Andrew Lever
Keyword(s):  
Structural Analysis ◽  
Secondary Structure ◽  
Rna Structure ◽  
Rna Secondary Structure ◽  
Biological Systems ◽  
Present Review ◽  
Structure Probing ◽  
Recent Advances ◽  
Near Future

The range of roles played by structured RNAs in biological systems is vast. At the same time as we are learning more about the importance of RNA structure, recent advances in reagents, methods and technology mean that RNA secondary structural probing has become faster and more accurate. As a result, the capabilities of laboratories that already perform this type of structural analysis have increased greatly, and it has also become more widely accessible. The present review summarizes established and recently developed techniques. The information we can derive from secondary structural analysis is assessed, together with the areas in which we are likely to see exciting developments in the near future.

scholarly journals RASP: an atlas of transcriptome-wide RNA secondary structure probing data

2020 ◽  
Vol 49 (D1) ◽  
pp. D183-D191
Author(s):  
Pan Li ◽  
Xiaolin Zhou ◽  
Kui Xu ◽  
Qiangfeng Cliff Zhang
Keyword(s):  
Secondary Structure ◽  
Rna Structure ◽  
Rna Secondary Structure ◽  
Rna Virus ◽  
Complex Structures ◽  
Biological Processes ◽  
Rna Molecules ◽  
Structure Probing ◽  
Technological Developments ◽  
User Friendly

Abstract RNA molecules fold into complex structures that are important across many biological processes. Recent technological developments have enabled transcriptome-wide probing of RNA secondary structure using nucleases and chemical modifiers. These approaches have been widely applied to capture RNA secondary structure in many studies, but gathering and presenting such data from very different technologies in a comprehensive and accessible way has been challenging. Existing RNA structure probing databases usually focus on low-throughput or very specific datasets. Here, we present a comprehensive RNA structure probing database called RASP (RNA Atlas of Structure Probing) by collecting 161 deduplicated transcriptome-wide RNA secondary structure probing datasets from 38 papers. RASP covers 18 species across animals, plants, bacteria, fungi, and also viruses, and categorizes 18 experimental methods including DMS-seq, SHAPE-Seq, SHAPE-MaP, and icSHAPE, etc. Specially, RASP curates the up-to-date datasets of several RNA secondary structure probing studies for the RNA genome of SARS-CoV-2, the RNA virus that caused the on-going COVID-19 pandemic. RASP also provides a user-friendly interface to query, browse, and visualize RNA structure profiles, offering a shortcut to accessing RNA secondary structures grounded in experimental data. The database is freely available at http://rasp.zhanglab.net.

scholarly journals Differential Analysis of RNA Structure Probing Experiments at Nucleotide Resolution: Uncovering Regulatory Functions of RNA Structure

2021 ◽  
Author(s):  
Bo Yu ◽  
Pan Li ◽  
Qiangfeng Cliff Zhang ◽  
Lin Hou
Keyword(s):  
Secondary Structure ◽  
Rna Structure ◽  
Rna Secondary Structure ◽  
Detection Methods ◽  
Systematic Bias ◽  
Differential Analysis ◽  
Variable Regions ◽  
Next Generation Sequencing Technology ◽  
Structure Probing ◽  
Nucleotide Resolution

AbstractRNAs perform their function by forming specific structures, which can change across cellular conditions. Structure probing experiments combined with next generation sequencing technology have enabled transcriptome-wide analysis of RNA secondary structure in various cellular conditions. Differential analysis of structure probing data in different conditions can reveal the RNA structurally variable regions (SVRs), which is important for understanding RNA functions. Here, we propose DiffScan, a computational framework for normalization and differential analysis of structure probing data in high resolution. DiffScan preprocesses structure probing datasets to remove systematic bias, and then scans the transcripts to identify SVRs and adaptively determines their lengths and locations. The proposed approach is compatible with most structure probing platforms (e.g., icSHAPE, DMS-seq). When evaluated with simulated and benchmark datasets, DiffScan identifies structurally variable regions at nucleotide resolution, with substantial improvement in accuracy compared with existing SVR detection methods. Moreover, the improvement is robust when tested in multiple structure probing platforms. Application of DiffScan in a dataset of multi-subcellular RNA structurome identified multiple regions that form different structures in nucleus and cytoplasm, linking RNA structural variation to regulation of mRNAs encoding mitochondria-associated proteins. This work provides an effective tool for differential analysis of RNA secondary structure, reinforcing the power of structure probing experiments in deciphering the dynamic RNA structurome.

Therapeutic properties of organotin complexes with reference to their structural and environmental features

2017 ◽  
Vol 37 (2) ◽  
pp. 51-70 ◽  
Author(s):  
Muhammad Iqbal ◽  
Saqib Ali ◽  
Ali Haider ◽  
Nasir Khalid
Keyword(s):  
Mode Of Action ◽  
Therapeutic Potential ◽  
Biological Systems ◽  
Structural Features ◽  
Present Review ◽  
Environmental Features ◽  
Recent Advances ◽  
Target Sites ◽  
Therapeutic Properties ◽  
Modes Of Interaction

AbstractOrganotin complexes are being extensively studied and screened for their therapeutic potential. Although many recent advances and achievements in this field have been made, the exact mode of action of these complexes is yet to be unveiled. In the present review, an attempt has been made to correlate the therapeutic properties of organotin complexes with their structural features and the environment in which these interact with biological systems. The mechanism, various modes of interaction with biological systems, and physiological target sites of organotin complexes have been highlighted as well.

Predicting RNA Secondary Structure Using a Improved BPSO Based on Stem Combination

2013 ◽  
Vol 325-326 ◽  
pp. 1551-1554
Author(s):  
Yi Qi
Keyword(s):  
Secondary Structure ◽  
Sensitivity And Specificity ◽  
Rna Structure ◽  
Structure Prediction ◽  
Rna Secondary Structure ◽  
Experimental Results ◽  
New Method ◽  
Rna Structure Prediction ◽  
New Strategies

In this paper, we present an improved BPSO to predict RNA secondary structure to improve the performance with two new strategies. First one is to reduce the searching space of PSO through super stem set construction. Second is to modify the general BPSO updating process to settle stem permutation and combination problems. The experimental results show that the new method is effective for RNA structure prediction in terms of sensitivity and specificity by different sequence datasets including simple pseudoknot.

scholarly journals mRNA adenosine methylase (MTA) deposits m6A on pri-miRNAs to modulate miRNA biogenesis inArabidopsis thaliana

2020 ◽  
Vol 117 (35) ◽  
pp. 21785-21795 ◽  
Author(s):  
Susheel Sagar Bhat ◽  
Dawid Bielewicz ◽  
Tomasz Gulanicz ◽  
Zsuzsanna Bodi ◽  
Xiang Yu ◽  
...  
Keyword(s):  
Secondary Structure ◽  
Rna Polymerase ◽  
Rna Polymerase Ii ◽  
Rna Structure ◽  
Methylation Status ◽  
Mirna Biogenesis ◽  
Stem Loop ◽  
Structure Probing ◽  
Plant Transcriptome ◽  
Loop Regions

InArabidopsis thaliana, the METTL3 homolog, mRNA adenosine methylase (MTA) introducesN6-methyladenosine (m6A) into various coding and noncoding RNAs of the plant transcriptome. Here, we show that an MTA-deficient mutant (mta) has decreased levels of microRNAs (miRNAs) but accumulates primary miRNA transcripts (pri-miRNAs). Moreover, pri-miRNAs are methylated by MTA, and RNA structure probing analysis reveals a decrease in secondary structure within stem–loop regions of these transcripts inmtamutant plants. We demonstrate interaction between MTA and both RNA Polymerase II and TOUGH (TGH), a plant protein needed for early steps of miRNA biogenesis. Both MTA and TGH are necessary for efficient colocalization of the Microprocessor components Dicer-like 1 (DCL1) and Hyponastic Leaves 1 (HYL1) with RNA Polymerase II. We propose that secondary structure of miRNA precursors induced by their MTA-dependent m6A methylation status, together with direct interactions between MTA and TGH, influence the recruitment of Microprocessor to plant pri-miRNAs. Therefore, the lack of MTA inmtamutant plants disturbs pri-miRNA processing and leads to the decrease in miRNA accumulation. Furthermore, our findings reveal that reduced miR393b levels likely contributes to the impaired auxin response phenotypes ofmtamutant plants.

scholarly journals A comprehensive database of high-throughput sequencing-based RNA secondary structure probing data (Structure Surfer)

2016 ◽  
Vol 17 (1) ◽  
Author(s):  
Nathan D. Berkowitz ◽  
Ian M. Silverman ◽  
Daniel M. Childress ◽  
Hilal Kazan ◽  
Li-San Wang ◽  
...  
Keyword(s):  
Data Structure ◽  
Secondary Structure ◽  
High Throughput ◽  
Rna Secondary Structure ◽  
High Throughput Sequencing ◽  
Comprehensive Database ◽  
Structure Probing

scholarly journals Bioinformatic and Physical Characterizations of Genome-Scale Ordered RNA Structure in Mammalian RNA Viruses

2008 ◽  
Vol 82 (23) ◽  
pp. 11824-11836 ◽  
Author(s):  
Matthew Davis ◽  
Selena M. Sagan ◽  
John P. Pezacki ◽  
David J. Evans ◽  
Peter Simmonds
Keyword(s):  
Secondary Structure ◽  
Rna Structure ◽  
Rna Secondary Structure ◽  
Large Scale ◽  
Rna Viruses ◽  
Plant Viruses ◽  
Large Set ◽  
Conserved Sequence ◽  
Evolutionarily Conserved ◽  
Genome Scale

ABSTRACT By the analysis of thermodynamic RNA secondary structure predictions, we previously obtained evidence for evolutionarily conserved large-scale ordering of RNA virus genomes (P. Simmonds, A. Tuplin, and D. J. Evans, RNA 10:1337-1351, 2004). Genome-scale ordered RNA structure (GORS) was widely distributed in many animal and plant viruses, much greater in extent than RNA structures required for viral translation or replication, but in mammalian viruses was associated with host persistence. To substantiate the existence of large-scale RNA structure differences between viruses, a large set of alignments of mammalian RNA viruses and rRNA sequences as controls were examined by thermodynamic methods (to calculate minimum free energy differences) and by algorithmically independent RNAz and Pfold methods. These methods produced generally concordant results and identified substantial differences in the degrees of evolutionarily conserved, sequence order-dependent RNA secondary structure between virus genera and groups. A probe hybridization accessibility assay was used to investigate the physical nature of GORS. Transcripts of hepatitis C virus (HCV), hepatitis G virus/GB virus-C (HGV/GBV-C), and murine norovirus, which are predicted to be structured, were largely inaccessible to hybridization in solution, in contrast to the almost universal binding of probes to a range of unstructured virus transcripts irrespective of G+C content. Using atomic force microscopy, HCV and HGV/GBV-C RNA was visualized as tightly compacted prolate spheroids, while under the same experimental conditions the predicted unstructured poliovirus and rubella virus RNA were pleomorphic and had extensively single-stranded RNA on deposition. Bioinformatic and physical characterization methods both identified fundamental differences in the configurations of viral genomic RNA that may modify their interactions with host cell defenses and their ability to persist.

scholarly journals Quantitative high-throughput tests of ubiquitous RNA secondary structure prediction algorithms via RNA/protein binding

2019 ◽  
Author(s):  
Winston R. Becker ◽  
Inga Jarmoskaite ◽  
Kalli Kappel ◽  
Pavanapuresan P. Vaidyanathan ◽  
Sarah K. Denny ◽  
...  
Keyword(s):  
Secondary Structure ◽  
Protein Binding ◽  
Rna Structure ◽  
Structure Prediction ◽  
Rna Secondary Structure ◽  
Nearest Neighbor ◽  
Secondary Structure Prediction ◽  
Structural Features ◽  
Vast Number ◽  
Prediction Algorithms

AbstractNearest-neighbor (NN) rules provide a simple and powerful quantitative framework for RNA structure prediction that is strongly supported for canonical Watson-Crick duplexes from a plethora of thermodynamic measurements. Predictions of RNA secondary structure based on nearest-neighbor (NN) rules are routinely used to understand biological function and to engineer and control new functions in biotechnology. However, NN applications to RNA structural features such as internal and terminal loops rely on approximations and assumptions, with sparse experimental coverage of the vast number of possible sequence and structural features. To test to what extent NN rules accurately predict thermodynamic stabilities across RNAs with non-WC features, we tested their predictions using a quantitative high-throughput assay platform, RNA-MaP. Using a thermodynamic assay with coupled protein binding, we carried out equilibrium measurements for over 1000 RNAs with a range of predicted secondary structure stabilities. Our results revealed substantial scatter and systematic deviations between NN predictions and observed stabilities. Solution salt effects and incorrect or omitted loop parameters contribute to these observed deviations. Our results demonstrate the need to independently and quantitatively test NN computational algorithms to identify their capabilities and limitations. RNA-MaP and related approaches can be used to test computational predictions and can be adapted to obtain experimental data to improve RNA secondary structure and other prediction algorithms.Significance statementRNA secondary structure prediction algorithms are routinely used to understand, predict and design functional RNA structures in biology and biotechnology. Given the vast number of RNA sequence and structural features, these predictions rely on a series of approximations, and independent tests are needed to quantitatively evaluate the accuracy of predicted RNA structural stabilities. Here we measure the stabilities of over 1000 RNA constructs by using a coupled protein binding assay. Our results reveal substantial deviations from the RNA stabilities predicted by popular algorithms, and identify factors contributing to the observed deviations. We demonstrate the importance of quantitative, experimental tests of computational RNA structure predictions and present an approach that can be used to routinely test and improve the prediction accuracy.

scholarly journals RNA Secondary Structurome Revealed Distinct Thermoregulation in Plasmodium falciparum

2022 ◽  
Vol 9 ◽  
Author(s):  
Yanwei Qi ◽  
Yuhong Zhang ◽  
Quankai Mu ◽  
Guixing Zheng ◽  
Mengxin Zhang ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Secondary Structure ◽  
Rna Structure ◽  
Rna Secondary Structure ◽  
Structural Changes ◽  
Environmental Changes ◽  
Parasite Development ◽  
Temperature Dependent ◽  
Trophozoite Stage ◽  
Temperature Changes

The development of Plasmodium parasites, a causative agent of malaria, requests two hosts and the completion of 11 different parasite stages during development. Therefore, an efficient and fast response of parasites to various complex environmental changes, such as ambient temperature, pH, ions, and nutrients, is essential for parasite development and survival. Among many of these environmental changes, temperature is a decisive factor for parasite development and pathogenesis, including the thermoregulation of rRNA expression, gametogenesis, and parasite sequestration in cerebral malaria. However, the exact mechanism of how Plasmodium parasites rapidly respond and adapt to temperature change remains elusive. As a fundamental and pervasive regulator of gene expression, RNA structure can be a specific mechanism for fine tuning various biological processes. For example, dynamic and temperature-dependent changes in RNA secondary structures can control the expression of different gene programs, as shown by RNA thermometers. In this study, we applied the in vitro and in vivo transcriptomic-wide secondary structurome approach icSHAPE to measure parasite RNA structure changes with temperature alteration at single-nucleotide resolution for ring and trophozoite stage parasites. Among 3,000 probed structures at different temperatures, our data showed structural changes in the global transcriptome, such as S-type rRNA, HRPII gene, and the erythrocyte membrane protein family. When the temperature drops from 37°C to 26°C, most of the genes in the trophozoite stage cause significantly more changes to the RNA structure than the genes in the ring stage. A multi-omics analysis of transcriptome data from RNA-seq and RNA structure data from icSHAPE reveals that the specific RNA secondary structure plays a significant role in the regulation of transcript expression for parasites in response to temperature changes. In addition, we identified several RNA thermometers (RNATs) that responded quickly to temperature changes. The possible thermo-responsive RNAs in Plasmodium falciparum were further mapped. To this end, we identified dynamic and temperature-dependent RNA structural changes in the P. falciparum transcriptome and performed a comprehensive characterization of RNA secondary structures over the course of temperature stress in blood stage development. These findings not only contribute to a better understanding of the function of the RNA secondary structure but may also provide novel targets for efficient vaccines or drugs.

scholarly journals Pervasive RNA Secondary Structure in the Genomes of SARS-CoV-2 and Other Coronaviruses

mBio ◽  
2020 ◽  
Vol 11 (6) ◽  
Author(s):  
P. Simmonds
Keyword(s):  
Secondary Structure ◽  
Rna Structure ◽  
Rna Secondary Structure ◽  
Large Scale ◽  
Rna Viruses ◽  
Shielding Effect ◽  
Cellular Interactions ◽  
Folding Energy ◽  
Base Pairing ◽  
Positive Strand Rna

ABSTRACT The ultimate outcome of the coronavirus disease 2019 (COVID-19) pandemic is unknown and is dependent on a complex interplay of its pathogenicity, transmissibility, and population immunity. In the current study, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was investigated for the presence of large-scale internal RNA base pairing in its genome. This property, termed genome-scale ordered RNA structure (GORS) has been previously associated with host persistence in other positive-strand RNA viruses, potentially through its shielding effect on viral RNA recognition in the cell. Genomes of SARS-CoV-2 were remarkably structured, with minimum folding energy differences (MFEDs) of 15%, substantially greater than previously examined viruses such as hepatitis C virus (HCV) (MFED of 7 to 9%). High MFED values were shared with all coronavirus genomes analyzed and created by several hundred consecutive energetically favored stem-loops throughout the genome. In contrast to replication-associated RNA structure, GORS was poorly conserved in the positions and identities of base pairing with other sarbecoviruses—even similarly positioned stem-loops in SARS-CoV-2 and SARS-CoV rarely shared homologous pairings, indicative of more rapid evolutionary change in RNA structure than in the underlying coding sequences. Sites predicted to be base paired in SARS-CoV-2 showed less sequence diversity than unpaired sites, suggesting that disruption of RNA structure by mutation imposes a fitness cost on the virus that is potentially restrictive to its longer evolution. Although functionally uncharacterized, GORS in SARS-CoV-2 and other coronaviruses represents important elements in their cellular interactions that may contribute to their persistence and transmissibility. IMPORTANCE The detection and characterization of large-scale RNA secondary structure in the genome of SARS-CoV-2 indicate an extraordinary and unsuspected degree of genome structural organization; this could be effectively visualized through a newly developed contour plotting method that displays positions, structural features, and conservation of RNA secondary structure between related viruses. Such RNA structure imposes a substantial evolutionary cost; paired sites showed greater restriction in diversity and represent a substantial additional constraint in reconstructing its molecular epidemiology. Its biological relevance arises from previously documented associations between possession of structured genomes and persistence, as documented for HCV and several other RNA viruses infecting humans and mammals. Shared properties potentially conferred by large-scale structure in SARS-CoV-2 include increasing evidence for prolonged infections and induced immune dysfunction that prevents development of protective immunity. The findings provide an additional element to cellular interactions that potentially influences the natural history of SARS-CoV-2, its pathogenicity, and its transmission.

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