HIV-1 leader RNA dimeric interface revealed by NMR

Ganser, Laura R.; Al‐Hashimi, Hashim M.

doi:10.1073/pnas.1615789113

Cited by 4 publications

(4 citation statements)

References 21 publications

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“…Kissing hairpins (also known as kissing-loops or kissing stem-loops) are formed from the base-pairing between the loop of two stem-loops (Table 1 , Figure 1 ). Many kissing hairpins are related to virus replication or transcription (You and Rice, 2008 ; Ganser and Al-Hashimi, 2016 ).…”

Section: Viral Rna Structuresmentioning

confidence: 99%

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 Rna Structuresmentioning

confidence: 99%

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

Lim

Brown

2018

Front. Microbiol.

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“…NMR methods are used to monitor the mechanism of DIS conversion from the kissing to the extended duplex structure, as well as the temporal formation and discrimination of intermolecular contacts [ 212 , 221 , 222 ]. Differential behavior of imino protons identified nucleotide-specific unwinding events upon temperature- and NC-induced structural conversion [ 206 , 223 ].…”

Section: Rna Components Important For Genome Packagingmentioning

confidence: 99%

NMR Studies of Retroviral Genome Packaging

Boyd

Brown

et al. 2020

Viruses

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Nearly all retroviruses selectively package two copies of their unspliced RNA genomes from a cellular milieu that contains a substantial excess of non-viral and spliced viral RNAs. Over the past four decades, combinations of genetic experiments, phylogenetic analyses, nucleotide accessibility mapping, in silico RNA structure predictions, and biophysical experiments were employed to understand how retroviral genomes are selected for packaging. Genetic studies provided early clues regarding the protein and RNA elements required for packaging, and nucleotide accessibility mapping experiments provided insights into the secondary structures of functionally important elements in the genome. Three-dimensional structural determinants of packaging were primarily derived by nuclear magnetic resonance (NMR) spectroscopy. A key advantage of NMR, relative to other methods for determining biomolecular structure (such as X-ray crystallography), is that it is well suited for studies of conformationally dynamic and heterogeneous systems—a hallmark of the retrovirus packaging machinery. Here, we review advances in understanding of the structures, dynamics, and interactions of the proteins and RNA elements involved in retroviral genome selection and packaging that are facilitated by NMR.

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“…[8] However,t hese applicationshave mainly been limited to small RNA systems( < 50 nt;n t= nucleotides)o wing to severe spectralo verlap and line broadening,i na ddition to conformational heterogeneityi nl argerR NA species. [10] Ah ybrid solid-liquid phase transcription method allowing region-specific isotope labeling forR NA moleculesl arger than 50 nt was previously reported. However,t hese approaches have led to questions regarding whether the isolated sub-domains adopt the same structures, behave with the same dynamic properties, and carry out the same functions as those encoded by the full-length RNA molecules.…”

mentioning

confidence: 99%

“…However,t hese approaches have led to questions regarding whether the isolated sub-domains adopt the same structures, behave with the same dynamic properties, and carry out the same functions as those encoded by the full-length RNA molecules. [10] Ah ybrid solid-liquid phase transcription method allowing region-specific isotope labeling forR NA moleculesl arger than 50 nt was previously reported. [11] This, however,w as found to be highly sequence restrictive and generated very low yields for large RNA molecules.…”

mentioning

confidence: 99%

CCR5 RNA Pseudoknots: Residue and Site‐Specific Labeling correlate Internal Motions with microRNA Binding

Chen

Longhini

Nußbaumer

et al. 2018

Chemistry A European J

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Conformational dynamics of RNA molecules play a critical role in governing their biological functions. Measurements of RNA dynamic behavior sheds important light on sites that interact with their binding partners or cellular stimulators. However, such measurements using solution-state NMR are difficult for large RNA molecules (>70 nt; nt=nucleotides) owing to severe spectral overlap, homonuclear C scalar couplings, and line broadening. Herein, a strategic combination of solid-phase synthesis, site-specific isotopic labeled phosphoramidites, and enzymatic ligation is introduced. This approach allowed the position-specific insertion of isotopic probes into a 96 nt CCR5 RNA fragment. Accurate measurements of functional dynamics using the Carr-Purcell-Meiboom-Gill (CPMG) relaxation dispersion (RD) experiments enabled extraction of the exchange rates and populations of this RNA. NMR chemical shift perturbation analysis of the RNA/microRNA-1224 complex indicated that A90-C1' of the pseudoknot exhibits similar changes in chemical shift observed in the excited state. This work demonstrates the general applicability of a NMR-labeling strategy to probe functional RNA structural dynamics.

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HIV-1 leader RNA dimeric interface revealed by NMR

Cited by 4 publications

References 21 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

NMR Studies of Retroviral Genome Packaging

CCR5 RNA Pseudoknots: Residue and Site‐Specific Labeling correlate Internal Motions with microRNA Binding

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