High-resolution NMR structure of an RNA model system: the 14-mer cUUCGg tetraloop hairpin RNA

Nozinovic, Senada; Fürtig, Boris; Jonker, Hendrik R. A.; Richter, Christian; Schwalbe, Harald

doi:10.1093/nar/gkp956

Cited by 170 publications

(297 citation statements)

References 64 publications

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“…For the UUCG tetraloop studied here, RDCs are available for several types of bond vectors located on the nucleobases (C6H6, C8H8, and N1H1) and on the furanose rings (C1 ′ H1 ′ ) (Nozinovic et al 2010a). RDCs result from the incomplete averaging out of dipolar interactions in partially aligned samples and can provide information on the average orientation of dipolar bond vectors with respect to an alignment frame (Prestegard et al 2000;Bax et al 2001;de Alba and Tjandra 2002;Salmon et al 2014).…”

Section: Overall Structure and Dynamicsmentioning

confidence: 99%

“…The initial RNA structure was taken from the NMR structure deposited in PDB (ID: 2KOC) (Nozinovic et al 2010a). The 5 ′ terminal residue was capped with an additional triphosphate group to mimic the sequence used in most experiments used here as reference.…”

Section: Cross-correlated Relaxation Rates From Simulationmentioning

confidence: 99%

“…The UUCG tetraloop RNA hairpin considered here is unusually stable (Cheong et al 1990;Antao et al 1991), has been extensively studied by solution NMR (Akke et al 1997;Fürtig et al 2004;Duchardt and Schwalbe 2005;Vallurupalli and Kay;2005, Rinnenthal et al 2009Nozinovic et al 2010a) and offers an excellent opportunity to evaluate the structure and dynamical description afforded by MD simulations. NMR is a major source of structural and dynamical information on nucleic acids in solution (Latham et al 2005;Fürtig et al 2007;Shajani and Varani 2007;Cruz and Westhof 2009;Rinnenthal et al 2011;Bardaro and Varani 2012;Salmon et al 2014), and is broadly supported by other forms of spectroscopy (Abdelkafi et al 1998;Leulliot et al 1999;Schiemann et al 2003;Qin and Dieckmann 2004;Bokinsky and Zhuang 2005;Zhuang 2005;Solomatin et al 2010).…”

Section: Introductionmentioning

confidence: 99%

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Structural fidelity and NMR relaxation analysis in a prototype RNA hairpin

Giambaşu

York

Case

2015

RNA

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RNA hairpins are widespread and very stable motifs that contribute decisively to RNA folding and biological function. The GTP1G2C3A4C5U6U7C8G9G10U11G12C13C14 construct (with a central UUCG tetraloop) has been extensively studied by solution NMR, and offers and excellent opportunity to evaluate the structure and dynamical description afforded by molecular dynamics (MD) simulations. Here, we compare average structural parameters and NMR relaxation rates estimated from a series of multiple independent explicit solvent MD simulations using the two most recent RNA AMBER force fields ( ff99 and ff10). Predicted overall tumbling times are ∼20% faster than those inferred from analysis of NMR data and follow the same trend when temperature and ionic strength is varied. The Watson-Crick stem and the "canonical" UUCG loop structure are maintained in most simulations including the characteristic syn conformation along the glycosidic bond of G9, although some key hydrogen bonds in the loop are partially disrupted. Our analysis pinpoints G9-G10 backbone conformations as a locus of discrepancies between experiment and simulation. In general the results for the more recent force-field parameters ( ff10) are closer to experiment than those for the older ones ( ff99). This work provides a comprehensive and detailed comparison of state of the art MD simulations against a wide variety of solution NMR measurements.

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Section: Overall Structure and Dynamicsmentioning

confidence: 99%

Section: Cross-correlated Relaxation Rates From Simulationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Structural fidelity and NMR relaxation analysis in a prototype RNA hairpin

Giambaşu

York

Case

2015

RNA

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“…The majority of hairpin stems are capped by GNRA or UNCG tetranucleotide sequences-where N is any base and R is a purine (Cheong et al 2015;Hall 2015). These tetranucleotide loops adopt distinctive folds that involve extensive and well-described networks of hydrogen bonds and stacking interactions (Cheong et al 1990;Heus and Pardi 1991;Allain and Varani 1995;Jucker and Pardi 1995a;Jucker et al 1996;Ennifar et al 2000;Correll and Swinger 2003;Nozinovic et al 2010). For GNRA and UNCG loops, it is generally assumed that the sequence commands a unique fold.…”

Section: Introductionmentioning

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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“…The final ensemble of 10 structures (Supplemental Fig. S2) was refined in a shell of water molecules (Linge et al 2003;Nilges et al 2008;Nozinovic et al 2010).…”

Section: Structure Calculationsmentioning

confidence: 99%

The structure of the SOLE element of oskar mRNA

Simon

Masiewicz

Ephrussi

et al. 2015

RNA

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mRNA localization by active transport is a regulated process that requires association of mRNPs with protein motors for transport along either the microtubule or the actin cytoskeleton. oskar mRNA localization at the posterior pole of the Drosophila oocyte requires a specific mRNA sequence, termed the SOLE, which comprises nucleotides of both exon 1 and exon 2 and is assembled upon splicing. The SOLE folds into a stem-loop structure. Both SOLE RNA and the exon junction complex (EJC) are required for oskar mRNA transport along the microtubules by kinesin. The SOLE RNA likely constitutes a recognition element for a yet unknown protein, which either belongs to the EJC or functions as a bridge between the EJC and the mRNA. Here, we determine the solution structure of the SOLE RNA by Nuclear Magnetic Resonance spectroscopy. We show that the SOLE forms a continuous helical structure, including a few noncanonical base pairs, capped by a pentanucleotide loop. The helix displays a widened major groove, which could accommodate a protein partner. In addition, the apical helical segment undergoes complex dynamics, with potential functional significance.

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High-resolution NMR structure of an RNA model system: the 14-mer cUUCGg tetraloop hairpin RNA

Cited by 170 publications

References 64 publications

Structural fidelity and NMR relaxation analysis in a prototype RNA hairpin

Structural fidelity and NMR relaxation analysis in a prototype RNA hairpin

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

The structure of the SOLE element of oskar mRNA

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