Secondary Structure of a Conserved Domain in the Intron of Influenza A NS1 mRNA

Priore, Salvatore F.; Kierzek, Elżbieta; Kierzek, Ryszard; Baman, Jayson R.; Moss, William C.; Dela-Moss, Lumbini I.; Turner, Douglas H.

doi:10.1371/journal.pone.0070615

Cited by 27 publications

(39 citation statements)

References 44 publications

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“…Several functionally important structures have been predicted to fold in the central parts of influenza RNA segments, mostly in the positive-sense mRNA regions where a regulatory role of RNA folding is expected. In particular, functional RNA structures predicted near the splice sites of segments 7 and 8 and in the region containing start codons of alternate internal open reading frames of segment 2 were supported by phylogenetic analysis and shown to be folded in vitro 5678910111213. Some of the conserved structures in segments 7 and 8 were shown to affect splicing14.…”

mentioning

confidence: 83%

Subtype-specific structural constraints in the evolution of influenza A virus hemagglutinin genes

Gultyaev

Spronken

Richard

et al. 2016

Sci Rep

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The influenza A virus genome consists of eight RNA segments. RNA structures within these segments and complementary (cRNA) and protein-coding mRNAs may play a role in virus replication. Here, conserved putative secondary structures that impose significant evolutionary constraints on the gene segment encoding the surface glycoprotein hemagglutinin (HA) were investigated using available sequence data on tens of thousands of virus strains. Structural constraints were identified by analysis of covariations of nucleotides suggested to be paired by structure prediction algorithms. The significance of covariations was estimated by mutual information calculations and tracing multiple covariation events during virus evolution. Covariation patterns demonstrated that structured domains in HA RNAs were mostly subtype-specific, whereas some structures were conserved in several subtypes. The influence of RNA folding on virus replication was studied by plaque assays of mutant viruses with disrupted structures. The results suggest that over the whole length of the HA segment there are local structured domains which contribute to the virus fitness but individually are not essential for the virus. Existence of subtype-specific structured regions in the segments of the influenza A virus genome is apparently an important factor in virus evolution and reassortment of its genes.

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mentioning

confidence: 83%

Subtype-specific structural constraints in the evolution of influenza A virus hemagglutinin genes

Gultyaev

Spronken

Richard

et al. 2016

Sci Rep

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“…Isoenergetic microarrays are being used to probe sequences in influenza A that are predicted to fold into stable, conserved structures ( 66 – 69 ). In the presence of Mg +2 , the 3′-splice site of influenza A segment 7 mRNA is in equilibrium between a hairpin and a pseudoknot conformation.…”

Section: Developing Rna-like and Isoenergetic Microarrays For Probingmentioning

confidence: 99%

Microarrays for identifying binding sites and probing structure of RNAs

Kierzek

Turner

Kierzek

2014

Nucleic Acids Research

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124

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Oligonucleotide microarrays are widely used in various biological studies. In this review, application of oligonucleotide microarrays for identifying binding sites and probing structure of RNAs is described. Deep sequencing allows fast determination of DNA and RNA sequence. High-throughput methods for determination of secondary structures of RNAs have also been developed. Those methods, however, do not reveal binding sites for oligonucleotides. In contrast, microarrays directly determine binding sites while also providing structural insights. Microarray mapping can be used over a wide range of experimental conditions, including temperature, pH, various cations at different concentrations and the presence of other molecules. Moreover, it is possible to make universal microarrays suitable for investigations of many different RNAs, and readout of results is rapid. Thus, microarrays are used to provide insight into oligonucleotide sequences potentially able to interfere with biological function. Better understanding of structure–function relationships of RNA can be facilitated by using microarrays to find RNA regions capable to bind oligonucleotides. That information is extremely important to design optimal sequences for antisense oligonucleotides and siRNA because both bind to single-stranded regions of target RNAs.

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“…Changing between these two conformations places splicing regulatory elements into varying structural contexts, which has likely implications on segment 7 splicing. Another conserved structure occurs in the intron of segment 8 mRNA [ 14 ]. The function of this domain is unclear, but its proximity to the 5’ splice site makes it a possible intronic splicing enhancer/inhibitor.…”

Section: Introductionmentioning

confidence: 99%

A Conserved Secondary Structural Element in the Coding Region of the Influenza A Virus Nucleoprotein (NP) mRNA Is Important for the Regulation of Viral Proliferation

et al. 2015

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Influenza A virus is a threat to humans due to seasonal epidemics and infrequent, but dangerous, pandemics that lead to widespread infection and death. Eight segments of RNA constitute the genome of this virus and they encode greater than eight proteins via alternative splicing of coding (+)RNAs generated from the genomic (-)RNA template strand. RNA is essential in its life cycle. A bioinformatics analysis of segment 5, which encodes nucleoprotein, revealed a conserved structural motif in the (+)RNA. The secondary structure proposed by energy minimization and comparative analysis agrees with structure predicted based on experimental data using a 121 nucleotide in vitro RNA construct comprising an influenza A virus consensus sequence and also an entire segment 5 (+)RNA (strain A/VietNam/1203/2004 (H5N1)). The conserved motif consists of three hairpins with one being especially thermodynamically stable. The biological importance of this conserved secondary structure is supported in experiments using antisense oligonucleotides in cell line, which found that disruption of this motif led to inhibition of viral fitness. These results suggest that this conserved motif in the segment 5 (+)RNA might be a candidate for oligonucleotide-based antiviral therapy.

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Secondary Structure of a Conserved Domain in the Intron of Influenza A NS1 mRNA

Cited by 27 publications

References 44 publications

Subtype-specific structural constraints in the evolution of influenza A virus hemagglutinin genes

Subtype-specific structural constraints in the evolution of influenza A virus hemagglutinin genes

Microarrays for identifying binding sites and probing structure of RNAs

A Conserved Secondary Structural Element in the Coding Region of the Influenza A Virus Nucleoprotein (NP) mRNA Is Important for the Regulation of Viral Proliferation

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