Principles of RNA Base Pairing:  Structures and Energies of the Trans Watson−Crick/Sugar Edge Base Pairs

2005 ◽  
Vol 109 (22) ◽  
pp. 11399-11410 ◽  
Author(s):  
Judit E. Šponer ◽  
Nad'a Špačková ◽  
Jerzy Leszczynski ◽  
Jiří Šponer
Keyword(s):  
Base Pairing ◽  
Base Pairs

scholarly journals Base pairing structure in the poly d(G-T) double helix: wobble base pairs

1978 ◽  
Vol 5 (6) ◽  
pp. 1955-1970 ◽  
Author(s):  
Thomas A. Early ◽  
John Olmsted ◽  
David R. Kearns ◽  
Axel G. Lezius
Keyword(s):  
Double Helix ◽  
Base Pairing ◽  
Base Pairs

Studies on the thymine–mercury–thymine base pairing in parallel and anti-parallel DNA duplexes

2015 ◽  
Vol 39 (11) ◽  
pp. 8752-8762 ◽  
Author(s):  
Gaofeng Liu ◽  
Zhiwen Li ◽  
Junfei Zhu ◽  
Yang Liu ◽  
Ying Zhou ◽  
...  
Keyword(s):  
Dna Duplexes ◽  
Base Pairing ◽  
Dna Duplex ◽  
Base Pairs ◽  
Thermal Stabilities

Parallel and anti-parallel T–Hg–T base pairs have different thermal stabilities and conformational influences on DNA duplex structures.

scholarly journals Protonation, Tautomerism, and Base Pairing of the Antiviral Favipiravir (T-705)

2020 ◽  
Author(s):  
Gabriel da Silva
Keyword(s):  
Density Functional ◽  
Enol Form ◽  
Free Energies ◽  
Base Pairing ◽  
Base Pairs ◽  
Functional Theory ◽  
Important Solution ◽  
Ring Nitrogen ◽  
Acidic Conditions ◽  
Gas Phase Basicities

Favipiravir (T-705) is an antiviral medication used to treat influenza. T-705 is also currently being trialled as a repurposed COVID-19 treatment. To help accelerate these efforts, this study provides important solution-phase properties of T-705 determined via computational chemistry. Density functional theory (DFT) calculations combined with the SMD continuum solvation model demonstrate that T-705 prefers the aromatic enol form in solution over the ketone tautomer. Deprotonation constants for the conjugate acids of T-705 (pKas) are then evaluated, by combining the DFT/SMD calculations with accurate G4 gas-phase basicities. These calculations indicate that T-705 is a weak base that should not significantly protonate at physiological pH. The preferential site for protonation is at the ring nitrogen ortho to the alcohol functional group (pKa ~ 7.4), followed by protonation of the oxygen on the amide side-chain at more acidic conditions (pKa ~ -9.8). Significantly, protonation of the ring nitrogen produces an acid that can deprotonate to the enol form (pKa ~ -5.1), providing a pathway for their interconversion. Finally, base-pairing of the active ribose-bound form of T-705 to cytidine and uridine is also examined. These calculations indicate that both base pairs have large binding free energies of around 4 – 5 kcal/mol, supporting previous findings that T-705 can bind with both nucleobases, leading to mis-incorporation of these pairs into viral RNA.<br>

scholarly journals The Topology of Hepatitis B Virus Pregenomic RNA Promotes Its Replication

2007 ◽  
Vol 81 (21) ◽  
pp. 11577-11584 ◽  
Author(s):  
Teresa M. Abraham ◽  
Daniel D. Loeb
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Previous Analysis ◽  
Acceptor Site ◽  
Minus Strand ◽  
Base Pairing ◽  
Base Pairs ◽  
B Virus ◽  
Template Switch ◽  
New Location

ABSTRACT Previous analysis of hepatitis B virus (HBV) indicated base pairing between two cis-acting sequences, the 5′ half of the upper stem of ε and φ, contributes to the synthesis of minus-strand DNA. Our goal was to identify other cis-acting sequences on the pregenomic RNA (pgRNA) involved in the synthesis of minus-strand DNA. We found that large portions of the pgRNA could be deleted or substituted without an appreciable decrease in the level of minus-strand DNA synthesized, indicating that most of the pgRNA is dispensable and that a specific size of the pgRNA is not required for this process. Our results indicated that the cis-acting sequences for the synthesis of minus-strand DNA are present near the 5′ and 3′ ends of the pgRNA. In addition, we found that the first-strand template switch could be directed to a new location when a 72-nucleotide (nt) fragment, which contained the cis-acting sequences present near the 3′ end of the pgRNA, was introduced at that location. Within this 72-nt region, we uncovered two new cis-acting sequences, which flank the acceptor site. We show that one of these sequences, named ω and located 3′ of the acceptor site, base pairs with φ to contribute to the synthesis of minus-strand DNA. Thus, base pairing between three cis-acting elements (5′ half of the upper stem of ε, φ, and ω) are necessary for the synthesis of HBV minus-strand DNA. We propose that this topology of pgRNA facilitates first-strand template switch and/or the initiation of synthesis of minus-strand DNA.

Enzymatic synthesis of ligand-bearing DNAs for metal-mediated base pairing utilising a template-independent polymerase

2016 ◽  
Vol 52 (19) ◽  
pp. 3762-3765 ◽  
Author(s):  
Teruki Kobayashi ◽  
Yusuke Takezawa ◽  
Akira Sakamoto ◽  
Mitsuhiko Shionoya
Keyword(s):  
Dna Polymerase ◽  
Enzymatic Synthesis ◽  
Base Pairing ◽  
Base Pairs ◽  
Dna Oligomers ◽  
Artificial Dna

Ligand-bearing artificial DNA oligomers that form metal-mediated base pairs were enzymatically synthesised by utilising a template-independent DNA polymerase.

scholarly journals RNA base pairing complexity in living cells visualized by correlated chemical probing

2019 ◽  
Author(s):  
Anthony M. Mustoe ◽  
Nicole Lama ◽  
Patrick S. Irving ◽  
Samuel W. Olson ◽  
Kevin M. Weeks
Keyword(s):  
Single Molecule ◽  
Rna Structure ◽  
Dimethyl Sulfate ◽  
Detection Methods ◽  
Base Pairing ◽  
Base Pairs ◽  
Chemical Probing ◽  
Pairing Interactions ◽  
In Cells

ABSTRACTRNA structure and dynamics are critical to biological function. However, strategies for determining RNA structure in vivo are limited, with established chemical probing and newer duplex detection methods each having notable deficiencies. Here we convert the common reagent dimethyl sulfate (DMS) into a useful probe of all four RNA nucleotides. Building on this advance, we introduce PAIR-MaP, which uses single-molecule correlated chemical probing to directly detect base pairing interactions in cells. PAIR-MaP has superior resolution and accuracy compared to alternative experiments, can resolve alternative pairing interactions of structurally dynamic RNAs, and enables highly accurate structure modeling, including of RNAs containing multiple pseudoknots and extensively bound by proteins. Application of PAIR-MaP to human RNase MRP and two bacterial mRNA 5'-UTRs reveals new functionally important and complex structures undetectable by conventional analyses. PAIR-MaP is a powerful, experimentally concise, and broadly applicable strategy for directly visualizing RNA base pairs and dynamics in cells.

scholarly journals Accurate inference of the full base-pairing structure of RNA by deep mutational scanning and covariation-induced deviation of activity

2019 ◽  
Author(s):  
Zhe Zhang ◽  
Peng Xiong ◽  
Tongchuan Zhang ◽  
Junfeng Wang ◽  
Jian Zhan ◽  
...  
Keyword(s):  
Human Genome ◽  
Structure Determination ◽  
False Positive ◽  
3D Structure ◽  
Noncoding Rnas ◽  
High Accuracy ◽  
Base Pairing ◽  
Base Pairs ◽  
3D Structure Determination ◽  
Covariation Analysis

ABSTRACTDespite the transcription of noncoding RNAs in 75% of the human genome and their roles in many diseases include cancer, we know very little about them due to lack of structural clues. The centerpiece of the structural clues is the full RNA base-pairing structure of secondary and tertiary contacts that can be precisely obtained only from costly and inefficient 3D structure determination. Here, we performed deep mutational scanning of self-cleaving CPEB3 ribozyme by error-prone PCR and showed that a library of <5×104 single-to-triple mutants is sufficient to infer all 26 including nonhelical and noncanonical base pairs at the precision of a single false positive. The accurate inference, further confirmed by a twister ribozyme, is resulted from covariation analysis by utilizing both functional and nonfunctional variants for unsupervised learning, followed by restrained optimization. The result highlights the usefulness of deep mutational scanning for high-accuracy structural inference.

scholarly journals Transformation of Saccharomyces cerevisiae with nonhomologous DNA: illegitimate integration of transforming DNA into yeast chromosomes and in vivo ligation of transforming DNA to mitochondrial DNA sequences

1993 ◽  
Vol 13 (5) ◽  
pp. 2697-2705
Author(s):  
R H Schiestl ◽  
M Dominska ◽  
T D Petes
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Mitochondrial Dna ◽  
Dna Sequences ◽  
Topoisomerase I ◽  
Target Sequence ◽  
Base Pairing ◽  
Base Pairs ◽  
Yeast Saccharomyces Cerevisiae ◽  
Dna Fragment

When the yeast Saccharomyces cerevisiae was transformed with DNA that shares no homology to the genome, three classes of transformants were obtained. In the most common class, the DNA was inserted as the result of a reaction that appears to require base pairing between the target sequence and the terminal few base pairs of the transforming DNA fragment. In the second class, no such homology was detected, and the transforming DNA was integrated next to a CTT or GTT in the target; it is likely that these integration events were mediated by topoisomerase I. The final class involved the in vivo ligation of transforming DNA with nucleus-localized linear fragments of mitochondrial DNA.

scholarly journals Accurate inference of the full base-pairing structure of RNA by deep mutational scanning and covariation-induced deviation of activity

2019 ◽  
Vol 48 (3) ◽  
pp. 1451-1465 ◽  
Author(s):  
Zhe Zhang ◽  
Peng Xiong ◽  
Tongchuan Zhang ◽  
Junfeng Wang ◽  
Jian Zhan ◽  
...  
Keyword(s):  
3D Structure ◽  
Noncoding Rnas ◽  
Unsupervised Classification ◽  
Base Pairing ◽  
Base Pairs ◽  
False Negatives ◽  
Epistasis Analysis ◽  
Direct Coupling Analysis ◽  
3D Structure Determination ◽  
Noncanonical Base Pairs

Abstract Despite the large number of noncoding RNAs in human genome and their roles in many diseases include cancer, we know very little about them due to lack of structural clues. The centerpiece of the structural clues is the full RNA base-pairing structure of secondary and tertiary contacts that can be precisely obtained only from costly and time-consuming 3D structure determination. Here, we performed deep mutational scanning of self-cleaving CPEB3 ribozyme by error-prone PCR and showed that a library of &lt;5 × 104 single-to-triple mutants is sufficient to infer 25 of 26 base pairs including non-nested, nonhelical, and noncanonical base pairs with both sensitivity and precision at 96%. Such accurate inference was further confirmed by a twister ribozyme at 100% precision with only noncanonical base pairs as false negatives. The performance was resulted from analyzing covariation-induced deviation of activity by utilizing both functional and nonfunctional variants for unsupervised classification, followed by Monte Carlo (MC) simulated annealing with mutation-derived scores. Highly accurate inference can also be obtained by combining MC with evolution/direct coupling analysis, R-scape or epistasis analysis. The results highlight the usefulness of deep mutational scanning for high-accuracy structural inference of self-cleaving ribozymes with implications for other structured RNAs that permit high-throughput functional selections.

Improved RNA secondary structure and tertiary base-pairing prediction using evolutionary profile, mutational coupling and two-dimensional transfer learning

2021 ◽  
Author(s):  
Jaswinder Singh ◽  
Kuldip Paliwal ◽  
Tongchuan Zhang ◽  
Jaspreet Singh ◽  
Thomas Litfin ◽  
...  
Keyword(s):  
High Resolution ◽  
Secondary Structure ◽  
Transfer Learning ◽  
Rna Secondary Structure ◽  
Computational Prediction ◽  
Supplementary Information ◽  
Base Pairing ◽  
Base Pairs ◽  
Homologous Sequences ◽  
Non Coding Rnas

Abstract Motivation The recent discovery of numerous non-coding RNAs (long non-coding RNAs, in particular) has transformed our perception about the roles of RNAs in living organisms. Our ability to understand them, however, is hampered by our inability to solve their secondary and tertiary structures in high resolution efficiently by existing experimental techniques. Computational prediction of RNA secondary structure, on the other hand, has received much-needed improvement, recently, through deep learning of a large approximate data, followed by transfer learning with gold-standard base-pairing structures from high-resolution 3-D structures. Here, we expand this single-sequence-based learning to the use of evolutionary profiles and mutational coupling. Results The new method allows large improvement not only in canonical base-pairs (RNA secondary structures) but more so in base-pairing associated with tertiary interactions such as pseudoknots, non-canonical and lone base-pairs. In particular, it is highly accurate for those RNAs of more than 1000 homologous sequences by achieving &gt;0.8 F1-score (harmonic mean of sensitivity and precision) for 14/16 RNAs tested. The method can also significantly improve base-pairing prediction by incorporating artificial but functional homologous sequences generated from deep mutational scanning without any modification. The fully automatic method (publicly available as server and standalone software) should provide the scientific community a new powerful tool to capture not only the secondary structure but also tertiary base-pairing information for building three-dimensional models. It also highlights the future of accurately solving the base-pairing structure by using a large number of natural and/or artificial homologous sequences. Availability and implementation Standalone-version of SPOT-RNA2 is available at https://github.com/jaswindersingh2/SPOT-RNA2. Direct prediction can also be made at https://sparks-lab.org/server/spot-rna2/. The datasets used in this research can also be downloaded from the GITHUB and the webserver mentioned above. Supplementary information Supplementary data are available at Bioinformatics online.

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