scholarly journals Structural Insights Into the 5′UG/3′GU Wobble Tandem in Complex With Ba2+ Cation

2022 ◽  
Vol 8 ◽  
Author(s):  
Agnieszka Ruszkowska ◽  
Ya Ying Zheng ◽  
Song Mao ◽  
Milosz Ruszkowski ◽  
Jia Sheng
Keyword(s):  
Electrostatic Potential ◽  
Metal Binding ◽  
Single Pair ◽  
Major Groove ◽  
Rna Structures ◽  
Rna Molecules ◽  
Rna Biology ◽  
Local Patch ◽  
Structural Insights ◽  
Unique Chemical

G•U wobble base pair frequently occurs in RNA structures. The unique chemical, thermodynamic, and structural properties of the G•U pair are widely exploited in RNA biology. In several RNA molecules, the G•U pair plays key roles in folding, ribozyme catalysis, and interactions with proteins. G•U may occur as a single pair or in tandem motifs with different geometries, electrostatics, and thermodynamics, further extending its biological functions. The metal binding affinity, which is essential for RNA folding, catalysis, and other interactions, differs with respect to the tandem motif type due to the different electrostatic potentials of the major grooves. In this work, we present the crystal structure of an RNA 8-mer duplex r[UCGUGCGA]2, providing detailed structural insights into the tandem motif I (5′UG/3′GU) complexed with Ba2+ cation. We compare the electrostatic potential of the presented motif I major groove with previously published structures of tandem motifs I, II (5′GU/3′UG), and III (5′GG/3′UU). A local patch of a strongly negative electrostatic potential in the major groove of the presented structure forms the metal binding site with the contributions of three oxygen atoms from the tandem. These results give us a better understanding of the G•U tandem motif I as a divalent metal binder, a feature essential for RNA functions.

scholarly journals Chemical and Enzymatic Probing of Viral RNAs: From Infancy to Maturity and Beyond

Viruses ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 1894
Author(s):  
Orian Gilmer ◽  
Erwan Quignon ◽  
Anne-Caroline Jousset ◽  
Jean-Christophe Paillart ◽  
Roland Marquet ◽  
...  
Keyword(s):  
Historical Perspective ◽  
Detection Methods ◽  
Rna Structures ◽  
Viral Rnas ◽  
Rna Molecules ◽  
Rna Biology ◽  
Key Players ◽  
The 1960S ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing

RNA molecules are key players in a variety of biological events, and this is particularly true for viral RNAs. To better understand the replication of those pathogens and try to block them, special attention has been paid to the structure of their RNAs. Methods to probe RNA structures have been developed since the 1960s; even if they have evolved over the years, they are still in use today and provide useful information on the folding of RNA molecules, including viral RNAs. The aim of this review is to offer a historical perspective on the structural probing methods used to decipher RNA structures before the development of the selective 2′-hydroxyl acylation analyzed by primer extension (SHAPE) methodology and to show how they have influenced the current probing techniques. Actually, these technological breakthroughs, which involved advanced detection methods, were made possible thanks to the development of next-generation sequencing (NGS) but also to the previous works accumulated in the field of structural RNA biology. Finally, we will also discuss how high-throughput SHAPE (hSHAPE) paved the way for the development of sophisticated RNA structural techniques.

Roles of Escherichia coli ZinT in cobalt, mercury and cadmium resistance and structural insights into the metal binding mechanism

Metallomics ◽  
2016 ◽  
Vol 8 (3) ◽  
pp. 327-336 ◽  
Author(s):  
H. G. Colaço ◽  
P. E. Santo ◽  
P. M. Matias ◽  
T. M. Bandeiras ◽  
J. B. Vicente
Keyword(s):  
Escherichia Coli ◽  
Metal Binding ◽  
Binding Mechanism ◽  
Cadmium Resistance ◽  
Structural Insights

Structural-functional platform unravels new roles for ZinT in cobalt, mercury and cadmium resistance, providing clues into the metal binding mechanism.

scholarly journals Factorial study of the RNA-seq computational workflow identifies biases as technical gene signatures

2020 ◽  
Vol 2 (2) ◽  
Author(s):  
Joël Simoneau ◽  
Ryan Gosselin ◽  
Michelle S Scott
Keyword(s):  
Factorization Method ◽  
Rna Seq ◽  
Similar Sequence ◽  
Gene Group ◽  
Rna Molecules ◽  
Design Choice ◽  
Rna Biology ◽  
Computational Workflow ◽  
The Common ◽  
Genome Annotations

Abstract RNA-seq is a modular experimental and computational approach aiming in identifying and quantifying RNA molecules. The modularity of the RNA-seq technology enables adaptation of the protocol to develop new ways to explore RNA biology, but this modularity also brings forth the importance of methodological thoroughness. Liberty of approach comes with the responsibility of choices, and such choices must be informed. Here, we present an approach that identifies gene group-specific quantification biases in current RNA-seq software and references by processing datasets using diverse RNA-seq computational pipelines, and by decomposing these expression datasets with an independent component analysis matrix factorization method. By exploring the RNA-seq pipeline using this systemic approach, we identify genome annotations as a design choice that affects to the same extent quantification results as does the choice of aligners and quantifiers. We also show that the different choices in RNA-seq methodology are not independent, identifying interactions between genome annotations and quantification software. Genes were mainly affected by differences in their sequence, by overlapping genes and genes with similar sequence. Our approach offers an explanation for the observed biases by identifying the common features used differently by the software and references, therefore providing leads for the betterment of RNA-seq methodology.

scholarly journals Self-assembly of large RNA structures: learning from DNA nanotechnology

2016 ◽  
Vol 2 (1) ◽  
Author(s):  
Jaimie Marie Stewart ◽  
Elisa Franco
Keyword(s):  
Self Assembly ◽  
De Novo ◽  
Dna Nanotechnology ◽  
De Novo Design ◽  
Dna Nanostructures ◽  
Rna Structures ◽  
Functional Nanostructures ◽  
Rna And Dna ◽  
Unique Chemical

AbstractNucleic acid nanotechnology offers many methods to build self-assembled structures using RNA and DNA. These scaffolds are valuable in multiple applications, such as sensing, drug delivery and nanofabrication. Although RNA and DNA are similar molecules, they also have unique chemical and structural properties. RNA is generally less stable than DNA, but it folds into a variety of tertiary motifs that can be used to produce complex and functional nanostructures. Another advantage of using RNA over DNA is its ability to be encoded into genes and to be expressed in vivo. Here we review existing approaches for the self-assembly of RNA and DNA nanostructures and specifically methods to assemble large RNA structures. We describe de novo design approaches used in DNA nanotechnology that can be ported to RNA. Lastly, we discuss some of the challenges yet to be solved to build micron-scale, multi stranded RNA scaffolds.

scholarly journals Novel Computational Method to Define RNA PSRs Explains Influenza A Virus Nucleotide Conservation

2018 ◽  
Author(s):  
Andrey Chursov ◽  
Nathan Fridlyand ◽  
Albert A. Sufianov ◽  
Oleg I. Kiselev ◽  
Irina Baranovskaya ◽  
...  
Keyword(s):  
Influenza A Virus ◽  
Influenza A ◽  
H1n1 Influenza ◽  
Computational Method ◽  
Structural Elements ◽  
Rna Structures ◽  
Stem Loop ◽  
Rna Molecules ◽  
Stem Loop Structure ◽  
Evolutionarily Conserved

ABSTRACTRNA molecules often fold into evolutionarily selected functional structures. Yet, the literature offers neither a satisfactory definition for “structured RNA regions”, nor a computational method to accurately identify such regions. Here, we define structured RNA regions based on the premise that both stems and loops in functional RNA structures should be conserved among RNA molecules sharing high sequence homology. In addition, we present a computational approach to identify RNA regions possessing evolutionarily conserved secondary structures, RNA ISRAEU (RNA Identification of Structured Regions As Evolutionary Unchanged). Applying this method to H1N1 influenza mRNAs revealed previously unknown structured RNA regions that are potentially essential for viral replication and/or propagation. Evolutionary conservation of RNA structural elements may explain, in part, why mutations in some nucleotide positions within influenza mRNAs occur significantly more often than in others. We found that mutations occurring in conserved nucleotide positions may be more disruptive for structured RNA regions than single nucleotide polymorphisms in positions that are more prone to changes. Finally, we predicted computationally a previously unknown stem-loop structure and demonstrated that oligonucleotides complementing the stem (but not the loop or unrelated sequences) reduce viral replicationin vitro.These results contribute to understanding influenza A virus evolution and can be applied to rational design of attenuated vaccines and/or drug designs based on disrupting conserved RNA structural elements.AUTHOR SUMMARYRNA structures play key biological roles. However, the literature offers neither a satisfactory definition for “structured RNA regions” nor the computational methodology to identify such regions. We define structured RNA regions based on the premise that functionally relevant RNA structures should be evolutionarily conserved, and devise a computational method to identify RNA regions possessing evolutionarily conserved secondary structural elements. Applying this method to influenza virus mRNAs of pandemic and seasonal H1N1 influenza A virus generated Predicted Structured Regions (PSRs), which were previously unknown. This explains the previously mysterious sequence conservation among evolving influenza strains. Also, we have experimentally supported existence of a computationally predicted stem-loop structure predicted computationally. Our approach may be useful in designing live attenuated influenza vaccines and/or anti-viral drugs based on disrupting necessary conserved RNA structures.

scholarly journals N6-Methyladenosine Modification Opens a New Chapter in Circular RNA Biology

2021 ◽  
Vol 9 ◽  
Author(s):  
Jun Wu ◽  
Xin Guo ◽  
Yi Wen ◽  
Shangqing Huang ◽  
Xiaohui Yuan ◽  
...  
Keyword(s):  
Cellular Localization ◽  
Circular Rna ◽  
Regulatory Mechanisms ◽  
Circular Rnas ◽  
Biological Functions ◽  
Future Directions ◽  
Rna Molecules ◽  
Physiological Processes ◽  
Rna Biology ◽  
Insight Into

As the most abundant internal modification in eukaryotic cells, N6-methyladenosine (m6A) in mRNA has shown widespread regulatory roles in a variety of physiological processes and disease progressions. Circular RNAs (circRNAs) are a class of covalently closed circular RNA molecules and play an essential role in the pathogenesis of various diseases. Recently, accumulating evidence has shown that m6A modification is widely existed in circRNAs and found its key biological functions in regulating circRNA metabolism, including biogenesis, translation, degradation and cellular localization. Through regulating circRNAs, studies have shown the important roles of m6A modification in circRNAs during immunity and multiple diseases, which represents a new layer of control in physiological processes and disease progressions. In this review, we focused on the roles played by m6A in circRNA metabolism, summarized the regulatory mechanisms of m6A-modified circRNAs in immunity and diseases, and discussed the current challenges to study m6A modification in circRNAs and the possible future directions, providing a comprehensive insight into understanding m6A modification of circRNAs in RNA epigenetics.

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