Solution structure of stem-loop α of the hepatitis B virus post-transcriptional regulatory element

Schwalbe, Martin; Ohlenschläger, Oliver; Marchanka, Alexander; Ramachandran, Ramadurai; Häfner, Sabine; Heise, Tilman; Görlach, Matthias

doi:10.1093/nar/gkn006

Cited by 30 publications

(27 citation statements)

References 81 publications

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“…It was inferred from NMR and thermodynamic measurements (Proctor et al 2002) as well as X-ray crystallography (Fig. 3E) that CNNG sequences can form either Z-turns-PDB code: 1ROQ- (Du et al 2003;Oberstrass et al 2006;Schwalbe et al 2008), or Z anti -turns. ′ atoms-in yellow-and the stacked nucleobase that are associated with oxygen-π contacts ≤3.5 Å (see Materials and Methods).…”

Section: Which Turns For Cnnn and Annn Sequences?mentioning

confidence: 99%

Revisiting GNRA and UNCG folds: U-turns versus Z-turns in RNA hairpin loops

D’Ascenzo¹,

Leonarski²,

Vicens³

et al. 2016

RNA

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When thinking about RNA three-dimensional structures, coming across GNRA and UNCG tetraloops is perceived as a boon since their folds have been extensively described. Nevertheless, analyzing loop conformations within RNA and RNP structures led us to uncover several instances of GNRA and UNCG loops that do not fold as expected. We noticed that when a GNRA does not assume its "natural" fold, it adopts the one we typically associate with a UNCG sequence. The same folding interconversion may occur for loops with UNCG sequences, for instance within tRNA anticodon loops. Hence, we show that some structured tetranucleotide sequences starting with G or U can adopt either of these folds. The underlying structural basis that defines these two fold types is the mutually exclusive stacking of a backbone oxygen on either the first (in GNRA) or the last nucleobase (in UNCG), generating an oxygen-π contact. We thereby propose to refrain from using sequences to distinguish between loop conformations. Instead, we suggest using descriptors such as U-turn (for "GNRA-type" folds) and a newly described Z-turn (for "UNCG-type" folds). Because tetraloops adopt for the largest part only two (inter)convertible turns, we are better able to interpret from a structural perspective loop interchangeability occurring in ribosomes and viral RNA. In this respect, we propose a general view on the inclination for a given sequence to adopt (or not) a specific fold. We also suggest how long-noncoding RNAs may adopt discrete but transient structures, which are therefore hard to predict.

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Section: Which Turns For Cnnn and Annn Sequences?mentioning

confidence: 99%

Revisiting GNRA and UNCG folds: U-turns versus Z-turns in RNA hairpin loops

D’Ascenzo¹,

Leonarski²,

Vicens³

et al. 2016

RNA

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“…Recent structural studies reveal that the gCAGG-(U)c tetraloop, another member of the gCNGG(N)c family of tetraloops, is quite accommodating of sequence variations with the two middle bases (corresponding to U48 and U49 in MHV SL2) found on the same or opposite sides of the structure; the nature of the stem-closing base pair also is variable, although typically it is a G-C base pair (36). This gCNGG(N) n c tetraloop structure bears significant similarity to the members of the yYNMGg tetraloop family (36), the most stable of which is the paradigm yUUCGg tetraloop (34). The yYNMGg tetraloop positions the N nucleotide (U48 in MHV) in roughly the same place as in the gCNGGc tetraloop, with the M base stacked on the 5Ј Y base on the opposite side of the loop.…”

Section: Vol 83 2009mentioning

confidence: 99%

Mouse Hepatitis Virus Stem-Loop 2 Adopts a uYNMG(U)a-Like Tetraloop Structure That Is Highly Functionally Tolerant of Base Substitutions

Liu

Keane

et al. 2009

J Virol

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Stem-loop 2 (SL2) of the 5-untranslated region of the mouse hepatitis virus (MHV) contains a highly conserved pentaloop (C47-U48-U49-G50-U51) stacked on a 5-bp stem. Solution nuclear magnetic resonance experiments are consistent with a 5-uYNMG(U)a or uCUYG(U)a tetraloop conformation characterized by an anti-C47-syn-G50 base-pairing interaction, with U51 flipped out into solution and G50 stacked on A52. Previous studies showed that U48C and U48A substitutions in MHV SL2 were lethal, while a U48G substitution was viable. Here, we characterize viruses harboring all remaining single-nucleotide substitutions in the pentaloop of MHV SL2 and also investigate the degree to which the sequence context of key pentaloop point mutations influences the MHV replication phenotype. U49 or U51 substitution mutants all are viable; C47 substitution mutants also are viable but produce slightly smaller plaques than wild-type virus. In contrast, G50A and G50C viruses are severely crippled and form much smaller plaques. Virus could not be recovered from G50U-containing mutants; rather, only true wild-type revertants or a virus, G50U/C47A, containing a second site mutation were recovered. These functional data suggest that the Watson-Crick edges of C47 and G50 (or A47 and U50 in the G50U/C47A mutant) are in close enough proximity to a hydrogen bond with U51 flipped out of the hairpin. Remarkably, increasing the helical stem stability rescues the previously lethal mutants U48C and G50U. These studies suggest that SL2 functions as an important, but rather plastic, structural element in stimulating subgenomic RNA synthesis in coronaviruses.Mouse hepatitis virus (MHV), a prototype group 2 coronavirus (CoV), is the most extensively studied CoV (26). CoVs are characterized by very large positive-sense RNA genomes of Ϸ30 kb, and during the course of replication they express seven to nine subgenomic RNAs (sgRNAs), each containing a common 3Ј-untranslated region (UTR) and 5Ј leader sequence, the latter of which is identical to the 5Ј end of the genomic RNA. The 3Ј end of the leader sequence contains a short (6-to 8-nucleotide [nt]) sequence, the transcriptional regulatory sequence (TRS-L), which also is present in the genome just 5Ј of the coding sequence for each subgenomic mRNA (TRS-B) (4). Among several models that have been proposed for CoV transcription and replication (2, 35, 38), the discontinuous transcription model during minus-strand synthesis is supported by significant accumulating genetic evidence (33,45,47,48). In this model, a set of 5Ј coterminal negative-strand sgRNAs are transcribed from positive-strand genomic RNA by the viral transcriptase/replicase complex (TRC), which then serve as templates for mRNAs synthesis. Genetic evidence is consistent with a process by which the complement to TRS-B on nascent or newly synthesized minus strands forms Watson-Crick base pairs with TRS-L within the 5ЈUTR of the genome to regulate mRNA synthesis (33,45,47,48).The biochemical details of sgRNA synthesis remain poorly understood. Since the ...

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“…The TAR RNA hairpin-loop structure from HIV-1 has been examined in the solid state to study motion within the structure, 822 and has also been solved bound to a TAR aptamer binding to the loop region. 823 Two CUGGpy structures have been solved which show stabilisation of the loop by a CG base pair across the loop, 824,825 backbone dynamics in a GCAA tetraloop have been examined using 13 C-labelling, 826 and the interconversion between duplex and hairpin from a Xist RNA A-repeat sequence has been reported. 827 The temperature-dependent dynamics in two YNMG tetraloops have been examined.…”

Section: Nmr Structuresmentioning

confidence: 99%

Nucleotides and Nucleic Acids; Oligo- and Polynucleotides

Loakes

2010

Organophosphorus Chemistry

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Solution structure of stem-loop α of the hepatitis B virus post-transcriptional regulatory element

Cited by 30 publications

References 81 publications

Revisiting GNRA and UNCG folds: U-turns versus Z-turns in RNA hairpin loops

Revisiting GNRA and UNCG folds: U-turns versus Z-turns in RNA hairpin loops

Mouse Hepatitis Virus Stem-Loop 2 Adopts a uYNMG(U)a-Like Tetraloop Structure That Is Highly Functionally Tolerant of Base Substitutions

Nucleotides and Nucleic Acids; Oligo- and Polynucleotides

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