Dataset Information

Investigation of Overhauser effects between pseudouridine and water protons in RNA helices.

ABSTRACT: The inherent chemical properties of RNA molecules are expanded by posttranscriptional modification of specific nucleotides. Pseudouridine (psi), the most abundant of the modified bases, features an additional imino group, NH1, as compared with uridine. When psi forms a Watson-Crick base pair with adenine in an RNA helix, NH1 is positioned within the major groove. The presence of psi often increases thermal stability of the helix or loop in which it is found [Hall, K. B. & McLaughlin, L. (1992) Nucleic Acids Res. 20, 1883-1889]. X-ray crystal structures of transfer RNAs [e.g., Arnez, J. & Steitz, T. (1994) Biochemistry 33, 7560-7567] have depicted water molecules bridging psiNH1 groups and nearby phosphate oxygen atoms, but direct evidence for this interaction in solution has not been acquired. Toward this end, we have used a rotating-frame Overhauser effect spectroscopy-type NMR pulse sequence with a CLEAN chemical-exchange spectroscopy spin-lock pulse train [Hwang, T.-L., Mori, S., Shaka, A. J. & van Zijl, P. C. M. (1997) J. Am. Chem. Soc. 119, 6203-6204] to test for psiNH1-water cross-relaxation effects within two RNA helices: (i) a complementary duplex, in which psi is not associated with structural change, and (ii) an RNA duplex representing the eukaryotic pre-mRNA branch-site helix from Saccharomyces cerevisiae, in which a conserved psi extrudes the branch-site adenosine from the helix. Our data implicate a water-psiNH1 hydrogen bond both in stabilizing the complementary helix and in favoring formation of the unique structure of the branch-site helix.

SUBMITTER: Newby MI

PROVIDER: S-EPMC130523 | biostudies-literature | 2002 Oct

REPOSITORIES: biostudies-literature

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Investigation of Overhauser effects between pseudouridine and water protons in RNA helices.

Newby Meredith I MI Greenbaum Nancy L NL

Proceedings of the National Academy of Sciences of the United States of America 20020919 20

The inherent chemical properties of RNA molecules are expanded by posttranscriptional modification of specific nucleotides. Pseudouridine (psi), the most abundant of the modified bases, features an additional imino group, NH1, as compared with uridine. When psi forms a Watson-Crick base pair with adenine in an RNA helix, NH1 is positioned within the major groove. The presence of psi often increases thermal stability of the helix or loop in which it is found [Hall, K. B. & McLaughlin, L. (1992) N ...[more]

PMID: 12242344

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Project description:Pseudouridine is one of the most abundant post-transcriptional modifications in RNA. We have previously shown that the FF99-derived parameters for pseudouridine and some of its naturally occurring derivatives in the AMBER distribution either alone or in combination with the revised γ torsion parameters (parmbsc0) failed to reproduce their conformational characteristics observed experimentally (Deb et al. in J Chem Inf Model 54:1129-1142, 2014; Deb et al. in J Comput Chem 37:1576-1588, 2016; Dutta et al. in J Chem Inf Model 60:4995-5002, 2020). However, the application of the recommended bsc0 correction did lead to an improvement in the description not only of the distribution in the γ torsional space but also of the sugar pucker distributions. In an earlier study, we examined the transferability of the revised glycosidic torsion parameters (χIDRP) for Ψ to its derivatives. We noticed that although these parameters in combination with the AMBER FF99-derived parameters and the revised γ torsional parameters resulted in conformational properties of these residues that were in better agreement with experimental observations, the sugar pucker distributions were still not reproduced accurately. Here we report a new set of partial atomic charges for pseudouridine, 1-methylpseudouridine, 3-methylpseudouridine and 2'-O-methylpseudouridine and a new set of glycosidic torsional parameters (χND) based on chosen glycosidic torsional profiles that most closely corresponded to the NMR data for conformational propensities and studied their effect on the conformational distributions using REMD simulations at the individual nucleoside level. We have also studied the effect of the choice of water model on the conformational characteristics of these modified nucleosides. Our observations suggest that the current revised set of parameters and partial atomic charges describe the sugar pucker distributions for these residues more accurately and that the choice of a suitable water model is important for the accurate description of their conformational properties. We have further validated the revised sets of parameters by studying the effect of substitution of uridine with pseudouridine within single stranded RNA oligonucleotides on their conformational and hydration characteristics.

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Dataset Information

Investigation of Overhauser effects between pseudouridine and water protons in RNA helices.

Publications

Investigation of Overhauser effects between pseudouridine and water protons in RNA helices.

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