Watson–Crick-like pairs in CCUG repeats: evidence for tautomeric shifts or protonation

Rypniewski, W.; Banaszak, K.; Kuliński, Tadeusz; Kiliszek, Agnieszka

doi:10.1261/rna.052399.115

Cited by 16 publications

(30 citation statements)

References 57 publications

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“…The 3D structure model of PAL1-PAL2 extended duplex suggests formation of non-canonical C-U intermolecular base-pairs involving U21 and C22 residues. Non-canonical C-U base pairs were identified in several biologically important RNAs and RNA duplexes containing the C-U base pairs can be considered similar to typical A-RNA helices [71,72]. The preservation of continuous stacking contributes significantly to the stability of RNA folds and minimizes the exposure of hydrophobic base surfaces to polar solvent.…”

Section: D Models Of Pal1-pal2 Interactions In Monomer and Dimermentioning

confidence: 99%

Retroviral-like determinants and functions required for dimerization of Ty1 retrotransposon RNA

et al. 2019

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During replication of long terminal repeat (LTR)-retrotransposons, their proteins and genome (g) RNA assemble into virus-like particles (VLPs) that are not infectious but functionally related to retroviral virions. Both virions and VLPs contain gRNA in a dimeric form, but contrary to retroviruses, little is known about how gRNA dimerization and packaging occurs in LTR-retrotransposons. The LTR-retrotransposon Ty1 from Saccharomyces cerevisiae is an informative model for studying LTR-retrotransposon and retrovirus replication. Using structural, mutational and functional analyses, we explored dimerization of Ty1 genomic RNA. We provide direct evidence that interactions of self-complementary PAL1 and PAL2 palindromic sequences localized within the 5′UTR are essential for Ty1 gRNA dimer formation. Mutations disrupting PAL1-PAL2 complementarity restricted RNA dimerization in vitro and Ty1 mobility in vivo. Although dimer formation and mobility of these mutants was inhibited, our work suggests that Ty1 RNA can dimerize via alternative contact points. In contrast to previous studies, we cannot confirm a role for PAL3, tRNAiMet as well as recently proposed initial kissing-loop interactions in dimer formation. Our data also supports the critical role of Ty1 Gag in RNA dimerization. Mature Ty1 Gag binds in the proximity of sequences involved in RNA dimerization and tRNAiMet annealing, but the 5′ pseudoknot in Ty1 RNA may constitute a preferred Gag-binding site. Taken together, these results expand our understanding of genome dimerization and packaging strategies utilized by LTR-retroelements.

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Section: D Models Of Pal1-pal2 Interactions In Monomer and Dimermentioning

confidence: 99%

Retroviral-like determinants and functions required for dimerization of Ty1 retrotransposon RNA

et al. 2019

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“…This type of pairing would not be possible if the N3 position were protonated, but possible C + C + pairs could form with two hydrogen bonds. There are several possible conformations for CC and CU pairs that would be disrupted by cytosine protonation (Kiliszek et al 2012;Rypniewski et al 2016). Cytidine protonation would also change stacking interactions.…”

Section: Proposed Model For Predicting the Free Energies Of Asymmetrimentioning

confidence: 99%

Advancing viral RNA structure prediction: measuring the thermodynamics of pyrimidine-rich internal loops

Phan

Mailey

Saeki

et al. 2017

RNA

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Accurate thermodynamic parameters improve RNA structure predictions and thus accelerate understanding of RNA function and the identification of RNA drug binding sites. Many viral RNA structures, such as internal ribosome entry sites, have internal loops and bulges that are potential drug target sites. Current models used to predict internal loops are biased toward small, symmetric purine loops, and thus poorly predict asymmetric, pyrimidine-rich loops with >6 nucleotides (nt) that occur frequently in viral RNA. This article presents new thermodynamic data for 40 pyrimidine loops, many of which can form UU or protonated CC base pairs. Uracil and protonated cytosine base pairs stabilize asymmetric internal loops. Accurate prediction rules are presented that account for all thermodynamic measurements of RNA asymmetric internal loops. New loop initiation terms for loops with >6 nt are presented that do not follow previous assumptions that increasing asymmetry destabilizes loops. Since the last 2004 update, 126 new loops with asymmetry or sizes greater than 2 × 2 have been measured. These new measurements significantly deepen and diversify the thermodynamic database for RNA. These results will help better predict internal loops that are larger, pyrimidine-rich, and occur within viral structures such as internal ribosome entry sites.

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“…C‐U cis Watson–Crick/Watson–Crick pair ( cWW ) pairs observed in CCUG repeats analyzed by Childs‐Disney et al (a and b) and Rypniewski et al (c) . Standard and tautomeric or protonated forms within the C–U pairs are shown on panel d. Water molecules (red spheres) are located in the minor groove.…”

Section: What We Have Learned From Crystallographic and Nmr Studies?mentioning

confidence: 98%

“…Noncanonical C‐U pairs are present in the structures of CCUG repeats . One of the available models contains three CCUG repeats adjacent to GAAA tetraloop/receptor motifs (PDB code: 4 K27) .…”

Section: What We Have Learned From Crystallographic and Nmr Studies?mentioning

confidence: 99%

Structures of RNA repeats associated with neurological diseases

2017

Self Cite

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All RNA molecules possess a 'propensity' to fold into complex secondary and tertiary structures. Although they are composed of only four types of nucleotides, they show an enormous structural richness which reflects their diverse functions in the cell. However, in some cases the folding of RNA can have deleterious consequences. Aberrantly expanded, repeated RNA sequences can exhibit gain-of-function abnormalities and become pathogenic, giving rise to many incurable neurological diseases. Most RNA repeats form long hairpin structures whose stem consists of noncanonical base pairs interspersed among Watson-Crick pairs. The expanded hairpins have an ability to sequester important proteins and form insoluble nuclear foci. The RNA pathology, common to many repeat disorders, has drawn attention to the structures of the RNA repeats. In this review, we summarize secondary structure probing and crystallographic studies of disease-related RNA repeat sequences. We discuss the unique structural features which can contribute to the pathogenic properties of the repeated runs. In addition, we present the newest reports concerning structural data linked to therapeutic approaches. WIREs RNA 2017, 8:e1412. doi: 10.1002/wrna.1412 For further resources related to this article, please visit the WIREs website.

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Watson–Crick-like pairs in CCUG repeats: evidence for tautomeric shifts or protonation

Cited by 16 publications

References 57 publications

Retroviral-like determinants and functions required for dimerization of Ty1 retrotransposon RNA

Retroviral-like determinants and functions required for dimerization of Ty1 retrotransposon RNA

Advancing viral RNA structure prediction: measuring the thermodynamics of pyrimidine-rich internal loops

Structures of RNA repeats associated with neurological diseases

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