The Influenza A PB1-F2 and N40 Start Codons Are Contained within an RNA Pseudoknot

Priore, Salvatore F.; Kauffmann, Andrew D.; Baman, Jayson R.; Turner, Douglas H.

doi:10.1021/bi501564d

Cited by 13 publications

(8 citation statements)

References 19 publications

(34 reference statements)

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“…Pseudoknots were predicted using DotKnot (Sperschneider and Datta, 2010 ). Notably, a predicted pseudoknot located in the virus segment 2 genome was subsequently shown to be consistent with that of chemical probing results (Priore et al, 2015 ). The predicted RNA structures near the splice junctions of M1/M2 and NS1/NEP transcripts were also validated experimentally and/or found to be important for the virus viability (Moss et al, 2012b ; Jiang et al, 2016 ).…”

Section: Viral Success Storiessupporting

confidence: 77%

Know Your Enemy: Successful Bioinformatic Approaches to Predict Functional RNA Structures in Viral RNAs

Lim

Brown

2018

Front. Microbiol.

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Structured RNA elements may control virus replication, transcription and translation, and their distinct features are being exploited by novel antiviral strategies. Viral RNA elements continue to be discovered using combinations of experimental and computational analyses. However, the wealth of sequence data, notably from deep viral RNA sequencing, viromes, and metagenomes, necessitates computational approaches being used as an essential discovery tool. In this review, we describe practical approaches being used to discover functional RNA elements in viral genomes. In addition to success stories in new and emerging viruses, these approaches have revealed some surprising new features of well-studied viruses e.g., human immunodeficiency virus, hepatitis C virus, influenza, and dengue viruses. Some notable discoveries were facilitated by new comparative analyses of diverse viral genome alignments. Importantly, comparative approaches for finding RNA elements embedded in coding and non-coding regions differ. With the exponential growth of computer power we have progressed from stem-loop prediction on single sequences to cutting edge 3D prediction, and from command line to user friendly web interfaces. Despite these advances, many powerful, user friendly prediction tools and resources are underutilized by the virology community.

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Section: Viral Success Storiessupporting

confidence: 77%

Know Your Enemy: Successful Bioinformatic Approaches to Predict Functional RNA Structures in Viral RNAs

Lim

Brown

2018

Front. Microbiol.

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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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“…Subsequent work challenged this finding 43 , however the significance of covariation in these RNAs remains a point of contention. Similarly, previous studies posited the existence of conserved structural elements which were (at least for IAV) subjected to subsequent structural probing 20 , 21 , 23 , 24 , 44 – 46 and functional analyses 13 , 14 , 17 – 19 , 22 , 25 , 31 . No motifs with statistical evidence of covariation were found in IAV, and the few hits we did observe were in ICV; indeed, the only motif with wide conservation (across clades) was found in ICV.…”

Section: Discussionmentioning

confidence: 82%

In silico analysis of local RNA secondary structure in influenza virus A, B and C finds evidence of widespread ordered stability but little evidence of significant covariation

Peterson

O’Leary

Moss

2022

Sci Rep

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Influenza virus is a persistent threat to human health; indeed, the deadliest modern pandemic was in 1918 when an H1N1 virus killed an estimated 50 million people globally. The intent of this work is to better understand influenza from an RNA-centric perspective to provide local, structural motifs with likely significance to the influenza infectious cycle for therapeutic targeting. To accomplish this, we analyzed over four hundred thousand RNA sequences spanning three major clades: influenza A, B and C. We scanned influenza segments for local secondary structure, identified/modeled motifs of likely functionality, and coupled the results to an analysis of evolutionary conservation. We discovered 185 significant regions of predicted ordered stability, yet evidence of sequence covariation was limited to 7 motifs, where 3—found in influenza C—had higher than expected amounts of sequence covariation.

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The Influenza A PB1-F2 and N40 Start Codons Are Contained within an RNA Pseudoknot

Cited by 13 publications

References 19 publications

Know Your Enemy: Successful Bioinformatic Approaches to Predict Functional RNA Structures in Viral RNAs

Know Your Enemy: Successful Bioinformatic Approaches to Predict Functional RNA Structures in Viral RNAs

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

In silico analysis of local RNA secondary structure in influenza virus A, B and C finds evidence of widespread ordered stability but little evidence of significant covariation

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