A GCUA tetranucleotide loop found in the poliovirus <i>ori</i>L by in vivo SELEX (un)expectedly forms a YNMG-like structure: Extending the YNMG family with GYYA

Melchers, Willem J. G.; Zoll, Jan; Tessari, Marco; Bakhmutov, Denis V.; Gmyl, Anatoly P.; Agol, Vadim I.; Heus, Hans A.

doi:10.1261/rna.113106

Cited by 17 publications

(31 citation statements)

References 65 publications

(77 reference statements)

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“…As noted above, the Z-turn GAAA loop capping helix 35a in the 50S of Haloarcula marismortui could exchange with YNMG sequences. Further, convincing evidence of sequence exchange that leads to similar folds has been reported in studies of viral RNA hairpins (Melchers et al 2006;Liu et al 2009;Zoll et al 2011;Clabbers et al 2014;Prostova et al 2015).…”

Section: Phylogenetic Considerations On Tetranucleotide Loops In Rnasupporting

confidence: 66%

“…Further evidence of an exchange between U-turns and Zturns originates from a combination of crystallographic and NMR data, which revealed that GNYA tetraloops-where Y is any pyrimidine-could fold like GNRA and adopt a Uturn since they can potentially form a 1-4 G•A t-SH pair (Melchers et al 2006). However, such loops are rare in X-ray structures.…”

Section: Gnra and Gnya Dimorphismmentioning

confidence: 99%

“…3C) has been reported, where the tetranucleotide sequence adopts a U-turn (Table 1). Yet, NMR experiments illustrated that a cGUUAg loop (Ihle et al 2005) and a uGCUAg loop (Melchers et al 2006) can adopt a Z-turn rather than the anticipated Uturn (PDB codes: 1Z30 and 2EVY).…”

Section: Gnra and Gnya Dimorphismmentioning

confidence: 99%

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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: Phylogenetic Considerations On Tetranucleotide Loops In Rnasupporting

confidence: 66%

Section: Gnra and Gnya Dimorphismmentioning

confidence: 99%

See 1 more Smart Citation

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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“…The principles of in vitro SELEX can be applied to in vivo evolution of viral RNAs, by randomizing a portion of viral sequence, introducing a pool of these randomized viral RNAs into host cells, and subsequently isolating functional RNAs. Melchers et al (14) recently used in nucleotides in the H4aϩH4b region of these boxed sequences denote differences between the related clones. Periods denote absence of a base in a recovered sequence.…”

Section: Discussionmentioning

confidence: 99%

Structural Plasticity and Rapid Evolution in a Viral RNA Revealed by In Vivo Genetic Selection

Guo

Lin

Zhang

et al. 2009

J Virol

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Satellite RNAs usually lack substantial homology with their helper viruses. The 356-nucleotide satC of Turnip crinkle virus (TCV) is unusual in that its 3-half shares high sequence similarity with the TCV 3 end. Computer modeling, structure probing, and/or compensatory mutagenesis identified four hairpins and three pseudoknots in this TCV region that participate in replication and/or translation. Two hairpins and two pseudoknots have been confirmed as important for satC replication. One portion of the related 3 end of satC that remains poorly characterized corresponds to juxtaposed TCV hairpins H4a and H4b and pseudoknot 3 , which are required for the TCV-specific requirement of translation (V. A. Stupina et al., RNA 14:2379-2393, 2008). Replacement of satC H4a with randomized sequence and scoring for fitness in plants by in vivo genetic selection (SELEX) resulted in winning sequences that contain an H4a-like stem-loop, which can have additional upstream sequence composing a portion of the stem. SELEX of the combined H4a and H4b region in satC generated three distinct groups of winning sequences. One group models into two stem-loops similar to H4a and H4b of TCV. However, the selected sequences in the other two groups model into single hairpins. Evolution of these single-hairpin SELEX winners in plants resulted in satC that can accumulate to wild-type (wt) levels in protoplasts but remain less fit in planta when competed against wt satC. These data indicate that two highly distinct RNA conformations in the H4a and H4b region can mediate satC fitness in protoplasts.Defective interfering (DI) and satellite (sat) RNAs are subviral RNAs that associate with viruses, require virus-encoded proteins for replication and other activities, and are capable of modifying viral infections. DI RNAs, found primarily in infections of animal hosts, are generated from viral genomic sequence, while satRNAs, more common to plant viruses, feature sequence that usually is unrelated to the helper virus. Most of the subviral RNAs with limited genome sizes are not translated, and thus their effect on virus infection must be mediated by the RNA primary or higher-ordered structure. DI and satRNAs that associate with different positive-strand RNA viruses can either intensify or attenuate viral symptoms (3, 10), which can involve inhibition of virus-encoded posttranscriptional gene silencing suppressors (9) or activation of posttranscriptional gene silencing (23).satRNAs and DI RNAs that share partial or near-complete sequence similarity with their helper virus contain related regions that allow for recognition by the helper virus RNAdependent RNA polymerase (RdRp). While this had led to the supposition that subviral RNAs would be useful models for examining replication elements that also exist in the much larger helper virus genome, more recent findings that RNA viruses contain elements in both their 5Ј and 3Ј untranslated regions that participate in translation (11,15,16), a function not required by small subviral RNAs, suggest that subvira...

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“…Molecular genetic and biochemical studies have identified residues of 3C required for RNA binding (1,3,18), and structural information for 3C has shown that residues required for RNA binding cluster on the same surface of 3C (27). Although structural information exists for some CRE subdomains, this information has not clarified the molecular basis for RNA recognition by 3C (8,9,20,22,26,29,40).…”

mentioning

confidence: 99%

Identification of the oriI-Binding Site of Poliovirus 3C Protein by Nuclear Magnetic Resonance Spectroscopy

Amero

Arnold

Moustafa

et al. 2008

J Virol

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Replication of picornaviral genomes requires recognition of at least three cis-acting replication elements: oriL, oriI, and oriR. Although these elements lack an obvious consensus sequence or structure, they are all recognized by the virus-encoded 3C protein. We have studied the poliovirus 3C-oriI interaction in order to begin to decipher the code of RNA recognition by picornaviral 3C proteins. oriI is a stem-loop structure that serves as the template for uridylylation of the peptide primer VPg by the viral RNA-dependent RNA polymerase. In this report, we have used nuclear magnetic resonance (NMR) techniques to study 3C alone and in complex with two single-stranded RNA oligonucleotides derived from the oriI stem. The 1 H-15 N spectra of 3C recorded in the presence of these RNAs revealed site-specific chemical shift perturbations. Residues that exhibit significant perturbations are primarily localized in the amino terminus and in a highly conserved loop between residues 81 and 89. In general, the RNA-binding site defined in this study is consistent with predictions based on biochemical and mutagenesis studies. Although some residues implicated in RNA binding by previous studies are perturbed in the 3C-RNA complex reported here, many are unique. These studies provide unique site-specific insight into residues of 3C that interact with RNA and set the stage for detailed structural investigation of the 3C-RNA complex by NMR. Interpretation of our results in the context of an intact oriI provides insight into the architecture of the picornavirus VPg uridylylation complex.Poliovirus (PV) is a small, nonenveloped virus with a singlestranded RNA (ssRNA) genome. PV is the best-studied member of the picornavirus family of viruses, which includes numerous viruses of medical importance, for example coxsackieviruses, human rhinoviruses, and hepatitis A virus. The genome contains a single open reading frame that encodes a large polyprotein that undergoes proteolytic cleavage to produce mature viral gene products. Polyprotein cleavage events are performed by one of two viral proteases: 2A and 3C. In addition to its major role as a proteinase, 3C and/or precursors thereof bind to cis-acting replication elements (CREs) located in the RNA genome (1,12,13,19,(30)(31)(32)(33)44).Three CREs are known. One CRE, located at the 5Ј end of the genome in the nontranslated region, adopts a cloverleaflike secondary structure (Fig. 1a and b). This element is often referred to as the cloverleaf (CL) or oriL (origin of replication left). Another CRE is located at the extreme 3Ј end, again in the nontranslated region, and consists of two stem-loop structures capable of forming a pseudoknot (Fig. 1a and b). This element is often referred to as oriR (origin of replication right). Finally, a CRE that consists of a single stem-loop exists within the 2C protein-coding sequence (Fig. 1a and b); an analogous CRE exists in all picornaviruses. While the exact position of this CRE varies, it is always located at an internal position of the genome. We will...

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A GCUA tetranucleotide loop found in the poliovirus oriL by in vivo SELEX (un)expectedly forms a YNMG-like structure: Extending the YNMG family with GYYA

Cited by 17 publications

References 65 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

Structural Plasticity and Rapid Evolution in a Viral RNA Revealed by In Vivo Genetic Selection

Identification of the oriI-Binding Site of Poliovirus 3C Protein by Nuclear Magnetic Resonance Spectroscopy

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