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Fulltext COGNAC: a web server for searching and annotating hydrogen-bonded base interactions in RNA three-dimensional structures

Firdaus-Raih M, Hamdani HY, Nadzirin N, Ramlan EI, Willett P, Artymiuk PJ

Nucleic Acids Res, 2014 Jul;42(Web Server issue):W382-8.
PMID: 24831543 DOI: 10.1093/nar/gku438

Hydrogen bonds are crucial factors that stabilize a complex ribonucleic acid (RNA) molecule's three-dimensional (3D) structure. Minute conformational changes can result in variations in the hydrogen bond interactions in a particular structure. Furthermore, networks of hydrogen bonds, especially those found in tight clusters, may be important elements in structure stabilization or function and can therefore be regarded as potential tertiary motifs. In this paper, we describe a graph theoretical algorithm implemented as a web server that is able to search for unbroken networks of hydrogen-bonded base interactions and thus provide an accounting of such interactions in RNA 3D structures. This server, COGNAC (COnnection tables Graphs for Nucleic ACids), is also able to compare the hydrogen bond networks between two structures and from such annotations enable the mapping of atomic level differences that may have resulted from conformational changes due to mutations or binding events. The COGNAC server can be accessed at http://mfrlab.org/grafss/cognac.

Matched MeSH terms: RNA/chemistry*
Fulltext InterRNA: a database of base interactions in RNA structures

Appasamy SD, Hamdani HY, Ramlan EI, Firdaus-Raih M

Nucleic Acids Res, 2016 Jan 4;44(D1):D266-71.
PMID: 26553798 DOI: 10.1093/nar/gkv1186

A major component of RNA structure stabilization are the hydrogen bonded interactions between the base residues. The importance and biological relevance for large clusters of base interactions can be much more easily investigated when their occurrences have been systematically detected, catalogued and compared. In this paper, we describe the database InterRNA (INTERactions in RNA structures database-http://mfrlab.org/interrna/) that contains records of known RNA 3D motifs as well as records for clusters of bases that are interconnected by hydrogen bonds. The contents of the database were compiled from RNA structural annotations carried out by the NASSAM (http://mfrlab.org/grafss/nassam) and COGNAC (http://mfrlab.org/grafss/cognac) computer programs. An analysis of the database content and comparisons with the existing corpus of knowledge regarding RNA 3D motifs clearly show that InterRNA is able to provide an extension of the annotations for known motifs as well as able to provide novel interactions for further investigations.

Matched MeSH terms: RNA/chemistry*
Correlation between polar surface area and bioferroelectricity in DNA and RNA nucleobases

Yam SC, Zain SM, Sanghiran Lee V, Chew KH

Eur Phys J E Soft Matter, 2018 Jul 18;41(7):86.
PMID: 30014219 DOI: 10.1140/epje/i2018-11696-5

We have performed computational molecular modelling to study the polarization switching and hysteresis loop behaviours of DNA and RNA nucleobases using the PM3 semi-empirical quantum mechanical approaches. All the nucleobases: adenine (A), thymine (T), guanine (G), cytosine (C), and uracil (U) were modelled. Our study indicates that all the nucleobases exhibit a zero-field polarization due to the presence of polar atoms or molecules such as amidogen and carbonyl. The shape of polarization P versus an applied electric field E hysteresis loop is square, implying typical ferroelectrics behaviour. The total energy U as a function of an applied electric field E exhibits a butterfly-like loop. The presence of zero-field polarization and ferroelectrics hysteresis loop behaviours in nucleobases may support the hypothesis of the existence of bioferroelectricity in DNA and RNA. We also found an interesting relationship between the minimum electric field required for switching [Formula: see text] and the ratio of the topological polar surface area (TPSA) to the total surface area (TSA) of a nucleobase. In particular, the [Formula: see text] of a nucleobase is inversely proportional to the TPSA/TSA ratio. This work may provide useful information for understanding the possible existence of ferroelectricity in biomaterials.

Matched MeSH terms: RNA/chemistry*
Fulltext NASSAM: a server to search for and annotate tertiary interactions and motifs in three-dimensional structures of complex RNA molecules

Hamdani HY, Appasamy SD, Willett P, Artymiuk PJ, Firdaus-Raih M

Nucleic Acids Res, 2012 Jul;40(Web Server issue):W35-41.
PMID: 22661578 DOI: 10.1093/nar/gks513

Similarities in the 3D patterns of RNA base interactions or arrangements can provide insights into their functions and roles in stabilization of the RNA 3D structure. Nucleic Acids Search for Substructures and Motifs (NASSAM) is a graph theoretical program that can search for 3D patterns of base arrangements by representing the bases as pseudo-atoms. The geometric relationship of the pseudo-atoms to each other as a pattern can be represented as a labeled graph where the pseudo-atoms are the graph's nodes while the edges are the inter-pseudo-atomic distances. The input files for NASSAM are PDB formatted 3D coordinates. This web server can be used to identify matches of base arrangement patterns in a query structure to annotated patterns that have been reported in the literature or that have possible functional and structural stabilization implications. The NASSAM program is freely accessible without any login requirement at http://mfrlab.org/grafss/nassam/.

Matched MeSH terms: RNA/chemistry*
A rapid and cost effective method in purifying small RNA

Citartan M, Tan SC, Tang TH

World J Microbiol Biotechnol, 2012 Jan;28(1):105-11.
PMID: 22806785 DOI: 10.1007/s11274-011-0797-0

Purification of RNA fragments from a complex mixture is a very common technique, and requires consideration of the time, cost, purity and yield of the purified RNA fragments. This study describes the fastest method of purifying small RNA with the lowest cost possible, without compromizing the yield and purity. The technique describes the purification of small RNA from polyacrylamide gel, resulting in a good yield of small RNA with minimum experimental steps in avoiding degradation of the RNA, obviating the use of ethidium bromide and phenol-chloroform extraction, as well as siliconized glass wools to remove the polyacrylamide gel particles. The purified small RNA is suitable for a wide variety of applications such as ligation, end labelling with radio isotope, RT-PCR (Reverse Transcriptase-PCR), Northern blotting, experimental RNomics study and also Systematic Evolution of Ligands by Exponential Enrichment (SELEX).

Matched MeSH terms: RNA/chemistry
Thermodynamic heuristics with case-based reasoning: combined insights for RNA pseudoknot secondary structure

Al-Khatib RM, Rashid NA, Abdullah R

J Biomol Struct Dyn, 2011 Aug;29(1):1-26.
PMID: 21696223

The secondary structure of RNA pseudoknots has been extensively inferred and scrutinized by computational approaches. Experimental methods for determining RNA structure are time consuming and tedious; therefore, predictive computational approaches are required. Predicting the most accurate and energy-stable pseudoknot RNA secondary structure has been proven to be an NP-hard problem. In this paper, a new RNA folding approach, termed MSeeker, is presented; it includes KnotSeeker (a heuristic method) and Mfold (a thermodynamic algorithm). The global optimization of this thermodynamic heuristic approach was further enhanced by using a case-based reasoning technique as a local optimization method. MSeeker is a proposed algorithm for predicting RNA pseudoknot structure from individual sequences, especially long ones. This research demonstrates that MSeeker improves the sensitivity and specificity of existing RNA pseudoknot structure predictions. The performance and structural results from this proposed method were evaluated against seven other state-of-the-art pseudoknot prediction methods. The MSeeker method had better sensitivity than the DotKnot, FlexStem, HotKnots, pknotsRG, ILM, NUPACK and pknotsRE methods, with 79% of the predicted pseudoknot base-pairs being correct.

Matched MeSH terms: RNA/chemistry*
Fulltext Graph Theoretical Methods and Workflows for Searching and Annotation of RNA Tertiary Base Motifs and Substructures

Emrizal R, Hamdani HY, Firdaus-Raih M

Int J Mol Sci, 2021 Aug 09;22(16).
PMID: 34445259 DOI: 10.3390/ijms22168553

The increasing number and complexity of structures containing RNA chains in the Protein Data Bank (PDB) have led to the need for automated structure annotation methods to replace or complement expert visual curation. This is especially true when searching for tertiary base motifs and substructures. Such base arrangements and motifs have diverse roles that range from contributions to structural stability to more direct involvement in the molecule's functions, such as the sites for ligand binding and catalytic activity. We review the utility of computational approaches in annotating RNA tertiary base motifs in a dataset of PDB structures, particularly the use of graph theoretical algorithms that can search for such base motifs and annotate them or find and annotate clusters of hydrogen-bond-connected bases. We also demonstrate how such graph theoretical algorithms can be integrated into a workflow that allows for functional analysis and comparisons of base arrangements and sub-structures, such as those involved in ligand binding. The capacity to carry out such automatic curations has led to the discovery of novel motifs and can give new context to known motifs as well as enable the rapid compilation of RNA 3D motifs into a database.

Matched MeSH terms: RNA/chemistry*
An analysis of simple computational strategies to facilitate the design of functional molecular information processors

Lee Y, Roslan R, Azizan S, Firdaus-Raih M, Ramlan EI

BMC Bioinformatics, 2016 Oct 28;17(1):438.
PMID: 27793081

BACKGROUND: Biological macromolecules (DNA, RNA and proteins) are capable of processing physical or chemical inputs to generate outputs that parallel conventional Boolean logical operators. However, the design of functional modules that will enable these macromolecules to operate as synthetic molecular computing devices is challenging.
RESULTS: Using three simple heuristics, we designed RNA sensors that can mimic the function of a seven-segment display (SSD). Ten independent and orthogonal sensors representing the numerals 0 to 9 are designed and constructed. Each sensor has its own unique oligonucleotide binding site region that is activated uniquely by a specific input. Each operator was subjected to a stringent in silico filtering. Random sensors were selected and functionally validated via ribozyme self cleavage assays that were visualized via electrophoresis.
CONCLUSIONS: By utilising simple permutation and randomisation in the sequence design phase, we have developed functional RNA sensors thus demonstrating that even the simplest of computational methods can greatly aid the design phase for constructing functional molecular devices.

Matched MeSH terms: RNA/chemistry*
Fulltext An alternate method for DNA and RNA extraction from clotted blood

Zakaria Z, Umi SH, Mokhtar SS, Mokhtar U, Zaiharina MZ, Aziz AT, et al.

Genet. Mol. Res., 2013;12(1):302-11.
PMID: 23408417 DOI: 10.4238/2013.February.4.4

We developed an alternative method to extract DNA and RNA from clotted blood for genomic and molecular investigations. A combination of the TRIzol method and the QIAamp spin column were used to extract RNA from frozen clotted blood. Clotted blood was sonicated and then the QIAamp DNA Blood Mini Kit was used for DNA extraction. Extracted DNA and RNA were adequate for gene expression analysis and copy number variation (CNV) genotyping, respectively. The purity of the extracted RNA and DNA was in the range of 1.8-2.0, determined by absorbance ratios of A(260):A(280). Good DNA and RNA integrity were confirmed using gel electrophoresis and automated electrophoresis. The extracted DNA was suitable for qPCR and microarrays for CNV genotyping, while the extracted RNA was adequate for gene analysis using RT-qPCR.

Matched MeSH terms: RNA/chemistry
Design of interacting multi-stable nucleic acids for molecular information processing

Ramlan EI, Zauner KP

Biosystems, 2011 Jul;105(1):14-24.
PMID: 21396427 DOI: 10.1016/j.biosystems.2011.02.006

Despite an exponential increase in computing power over the past decades, present information technology falls far short of expectations in areas such as cognitive systems and micro robotics. Organisms demonstrate that it is possible to implement information processing in a radically different way from what we have available in present technology, and that there are clear advantages from the perspective of power consumption, integration density, and real-time processing of ambiguous data. Accordingly, the question whether the current silicon substrate and associated computing paradigm is the most suitable approach to all types of computation has come to the fore. Macromolecular materials, so successfully employed by nature, possess uniquely promising properties as an alternate substrate for information processing. The two key features of macromolecules are their conformational dynamics and their self-assembly capabilities. The purposeful design of macromolecules capable of exploiting these features has proven to be a challenge, however, for some groups of molecules it is increasingly practicable. We here introduce an algorithm capable of designing groups self-assembling of nucleic acid molecules with multiple conformational states. Evaluation using natural and artificially designed nucleic acid molecules favours this algorithm significantly, as compared to the probabilistic approach. Furthermore, the thermodynamic properties of the generated candidates are within the same approximation as the customised trans-acting switching molecules reported in the laboratory.

Matched MeSH terms: RNA/chemistry
Fulltext In vitro antiviral activity of circular triple helix forming oligonucleotide RNA towards Feline Infectious Peritonitis virus replication

Choong OK, Mehrbod P, Tejo BA, Omar AR

Biomed Res Int, 2014;2014:654712.
PMID: 24707494 DOI: 10.1155/2014/654712

Feline Infectious Peritonitis (FIP) is a severe fatal immune-augmented disease in cat population. It is caused by FIP virus (FIPV), a virulent mutant strain of Feline Enteric Coronavirus (FECV). Current treatments and prophylactics are not effective. The in vitro antiviral properties of five circular Triple-Helix Forming Oligonucleotide (TFO) RNAs (TFO1 to TFO5), which target the different regions of virulent feline coronavirus (FCoV) strain FIPV WSU 79-1146 genome, were tested in FIPV-infected Crandell-Rees Feline Kidney (CRFK) cells. RT-qPCR results showed that the circular TFO RNAs, except TFO2, inhibit FIPV replication, where the viral genome copy numbers decreased significantly by 5-fold log10 from 10(14) in the virus-inoculated cells to 10(9) in the circular TFO RNAs-transfected cells. Furthermore, the binding of the circular TFO RNA with the targeted viral genome segment was also confirmed using electrophoretic mobility shift assay. The strength of binding kinetics between the TFO RNAs and their target regions was demonstrated by NanoITC assay. In conclusion, the circular TFOs have the potential to be further developed as antiviral agents against FIPV infection.

Matched MeSH terms: RNA/chemistry
An Overview of Circular RNAs

Awasthi R, Singh AK, Mishra G, Maurya A, Chellappan DK, Gupta G, et al.

Adv Exp Med Biol, 2018 9 28;1087:3-14.
PMID: 30259353 DOI: 10.1007/978-981-13-1426-1_1

Circular RNAs (cirRNAs) are long, noncoding endogenous RNA molecules and covalently closed continuous loop without 5'-3' polarity and polyadenylated tail which are largely concentrated in the nucleus. CirRNA regulates gene expression by modulating microRNAs and functions as potential biomarker. CirRNAs can translate in vivo to link between their expression and disease. They are resistant to RNA exonuclease and can convert to the linear RNA by microRNA which can then act as competitor to endogenous RNA. This chapter summarizes the evolutionary conservation and expression of cirRNAs, their identification, highlighting various computational approaches on cirRNA, and translation with a focus on the breakthroughs and the challenges in this new field.

Matched MeSH terms: RNA/chemistry
Fulltext Inducible RasGEF1B circular RNA is a positive regulator of ICAM-1 in the TLR4/LPS pathway

Ng WL, Marinov GK, Liau ES, Lam YL, Lim YY, Ea CK

RNA Biol, 2016 09;13(9):861-71.
PMID: 27362560 DOI: 10.1080/15476286.2016.1207036

Circular RNAs (circRNAs) constitute a large class of RNA species formed by the back-splicing of co-linear exons, often within protein-coding transcripts. Despite much progress in the field, it remains elusive whether the majority of circRNAs are merely aberrant splicing by-products with unknown functions, or their production is spatially and temporally regulated to carry out specific biological functions. To date, the majority of circRNAs have been cataloged in resting cells. Here, we identify an LPS-inducible circRNA: mcircRasGEF1B, which is predominantly localized in cytoplasm, shows cell-type specific expression, and has a human homolog with similar properties, hcircRasGEF1B. We show that knockdown of the expression of mcircRasGEF1B reduces LPS-induced ICAM-1 expression. Additionally, we demonstrate that mcircRasGEF1B regulates the stability of mature ICAM-1 mRNAs. These findings expand the inventory of functionally characterized circRNAs with a novel RNA species that may play a critical role in fine-tuning immune responses and protecting cells against microbial infection.

Matched MeSH terms: RNA/chemistry
Sequence and localization of kcnk10a in the brain of adult zebrafish (Danio rerio)

Loganathan K, Moriya S, Sivalingam M, Ng KW, Parhar IS

J. Chem. Neuroanat., 2017 Dec;86:92-99.
PMID: 29074372 DOI: 10.1016/j.jchemneu.2017.10.004

kcnk10a has been predicted in zebrafish to be a member of the two-pore domain potassium ion (K+) channel-related K+ (TREK) channel family known as a thermoreceptor. Since reproduction is affected by temperature, Kcnk10a could be involved in the regulation of reproduction. However, expression of kcnk10a in the zebrafish brain and association with reproduction has not been identified. In this study, the full length sequence and localization of kcnk10a in the brain was investigated and gene expressions of the TREK channel family were examined to investigate association with reproduction. We initially identified the full length cDNA sequence of kcnk10a using Rapid Amplification of cDNA Ends and localization in the zebrafish brain using in situ hybridization. Furthermore, we examined the gene expression differences of kcnk2b, kcnk10a and kcnk10b mRNA between genders as well as developmental stages by real-time PCR. The deduced amino acid sequence of the identified kcnk10a mRNA contains highly conserved two pore domains and four transmembrane regions and was higher similarity to zebrafish Kcnk10b than zebrafish Kcnk2a and 2b. kcnk10a mRNA was widely distributed in the brain such as the preoptic area, hypothalamus and the midbrain. kcnk10a mRNA expression exhibited significant difference between mature male and female, and increase during puberty. Kcnk10a could be involved in the regulation of reproductive function.

Matched MeSH terms: RNA/chemistry

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