Conformational properties and thermodynamics of the RNA duplex r(CGCAAAUUUGCG)2: Comparison with the DNA analogue d(CGCAAATTTGCG)2

Maria R. Conte; Graeme L. Conn; Tom Brown; Andrew N. Lane

doi:10.1093/nar/25.13.2627

Conformational properties and thermodynamics of the RNA duplex r(CGCAAAUUUGCG)₂: Comparison with the DNA analogue d(CGCAAATTTGCG)₂

Maria R. Conte
, Graeme L. Conn
, Tom Brown
, Andrew N. Lane

Producción científica: Article › revisión exhaustiva

42 Citas (Scopus)

Resumen

The thermodynamic stability of nine dodecamers (four DNA and five RNA) of the same base composition has been compared by UV-melting. The ΔG of stabilisation were in the order: r(GACUGAUCAGUC)₂ > r(CGCAAATTTGCG)₂ ≃ r(CGCAUAUAUGCG)₂ > d(CGCAAATTTGCG)₂ ≃ r(CGCAAAUUUGCG)₂ > d(CGCATATATGCG)₂ ≃ d(GACTGATCAGTC)₂ > r(CGCUUUAAAGCG)₂ ≃ d(CGCTTTAAAGCG)₂. Compared with the mixed sequences, both r(AAAUUU) and r(UUUAAA) are greatly destablising in RNA, whereas in DNA, d(TTTAAA) is destabilising but d(AAATTT) is stabilising, which has been attributed to the formation of a special B' structure involving large propeller twists of the A-T base pairs. The solution structure of the RNA dodecamer r(CGCAAAUUUGCG)₂ has been determined using NMR and restrained molecular dynamics calculations to assess the conformational reasons for its stability in comparison with d(CGCAAATTTGCG)₂. The structures refined to a mean pairwise r.m.s.d. of 0.89 ± 0.29 Å. The nucleotide conformations are typical of the A family of structures. However, although the helix axis displacement is ≃ 4.6 Å into the major groove, the rise (3.0 Å) and base inclination (≃ 6°) are different from standard A form RNA. The extensive base-stacking found in the AAATTT tract of the DNA homologue that is largely responsible for the higher thermodynamic stability of the DNA duplex is reduced in the RNA structure, which may account for its low relative stability.

Idioma original	English
Páginas (desde-hasta)	2627-2634
Número de páginas	8
Publicación	Nucleic Acids Research
Volumen	25
N.º	13
DOI	https://doi.org/10.1093/nar/25.13.2627
Estado	Published - jul 1 1997

Nota bibliográfica

Funding Information:
This work was supported by the Medical Research Council of the UK, and by grants to MRC from the Wellcome Trust and to GLC by the Royal Society of Edinburgh. We thank our colleagues for helpful discussions, and in particular Dr Mark Searle. NMR spectra were recorded at the MRC Biomedical NMR Facility.

Financiación

This work was supported by the Medical Research Council of the UK, and by grants to MRC from the Wellcome Trust and to GLC by the Royal Society of Edinburgh. We thank our colleagues for helpful discussions, and in particular Dr Mark Searle. NMR spectra were recorded at the MRC Biomedical NMR Facility.

Financiadores
Wellcome Trust
Medical Research Council
Royal Society of Edinburgh

ASJC Scopus subject areas

Genetics

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10.1093/nar/25.13.2627

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@article{2bb2767507af4746a4b423a5427d4c2f,

title = "Conformational properties and thermodynamics of the RNA duplex r(CGCAAAUUUGCG)2: Comparison with the DNA analogue d(CGCAAATTTGCG)2",

abstract = "The thermodynamic stability of nine dodecamers (four DNA and five RNA) of the same base composition has been compared by UV-melting. The ΔG of stabilisation were in the order: r(GACUGAUCAGUC)2 > r(CGCAAATTTGCG)2 ≃ r(CGCAUAUAUGCG)2 > d(CGCAAATTTGCG)2 ≃ r(CGCAAAUUUGCG)2 > d(CGCATATATGCG)2 ≃ d(GACTGATCAGTC)2 > r(CGCUUUAAAGCG)2 ≃ d(CGCTTTAAAGCG)2. Compared with the mixed sequences, both r(AAAUUU) and r(UUUAAA) are greatly destablising in RNA, whereas in DNA, d(TTTAAA) is destabilising but d(AAATTT) is stabilising, which has been attributed to the formation of a special B' structure involving large propeller twists of the A-T base pairs. The solution structure of the RNA dodecamer r(CGCAAAUUUGCG)2 has been determined using NMR and restrained molecular dynamics calculations to assess the conformational reasons for its stability in comparison with d(CGCAAATTTGCG)2. The structures refined to a mean pairwise r.m.s.d. of 0.89 ± 0.29 {\AA}. The nucleotide conformations are typical of the A family of structures. However, although the helix axis displacement is ≃ 4.6 {\AA} into the major groove, the rise (3.0 {\AA}) and base inclination (≃ 6°) are different from standard A form RNA. The extensive base-stacking found in the AAATTT tract of the DNA homologue that is largely responsible for the higher thermodynamic stability of the DNA duplex is reduced in the RNA structure, which may account for its low relative stability.",

author = "Conte, \{Maria R.\} and Conn, \{Graeme L.\} and Tom Brown and Lane, \{Andrew N.\}",

note = "Funding Information: This work was supported by the Medical Research Council of the UK, and by grants to MRC from the Wellcome Trust and to GLC by the Royal Society of Edinburgh. We thank our colleagues for helpful discussions, and in particular Dr Mark Searle. NMR spectra were recorded at the MRC Biomedical NMR Facility.",

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AU - Brown, Tom

AU - Lane, Andrew N.

N1 - Funding Information: This work was supported by the Medical Research Council of the UK, and by grants to MRC from the Wellcome Trust and to GLC by the Royal Society of Edinburgh. We thank our colleagues for helpful discussions, and in particular Dr Mark Searle. NMR spectra were recorded at the MRC Biomedical NMR Facility.

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N2 - The thermodynamic stability of nine dodecamers (four DNA and five RNA) of the same base composition has been compared by UV-melting. The ΔG of stabilisation were in the order: r(GACUGAUCAGUC)2 > r(CGCAAATTTGCG)2 ≃ r(CGCAUAUAUGCG)2 > d(CGCAAATTTGCG)2 ≃ r(CGCAAAUUUGCG)2 > d(CGCATATATGCG)2 ≃ d(GACTGATCAGTC)2 > r(CGCUUUAAAGCG)2 ≃ d(CGCTTTAAAGCG)2. Compared with the mixed sequences, both r(AAAUUU) and r(UUUAAA) are greatly destablising in RNA, whereas in DNA, d(TTTAAA) is destabilising but d(AAATTT) is stabilising, which has been attributed to the formation of a special B' structure involving large propeller twists of the A-T base pairs. The solution structure of the RNA dodecamer r(CGCAAAUUUGCG)2 has been determined using NMR and restrained molecular dynamics calculations to assess the conformational reasons for its stability in comparison with d(CGCAAATTTGCG)2. The structures refined to a mean pairwise r.m.s.d. of 0.89 ± 0.29 Å. The nucleotide conformations are typical of the A family of structures. However, although the helix axis displacement is ≃ 4.6 Å into the major groove, the rise (3.0 Å) and base inclination (≃ 6°) are different from standard A form RNA. The extensive base-stacking found in the AAATTT tract of the DNA homologue that is largely responsible for the higher thermodynamic stability of the DNA duplex is reduced in the RNA structure, which may account for its low relative stability.

AB - The thermodynamic stability of nine dodecamers (four DNA and five RNA) of the same base composition has been compared by UV-melting. The ΔG of stabilisation were in the order: r(GACUGAUCAGUC)2 > r(CGCAAATTTGCG)2 ≃ r(CGCAUAUAUGCG)2 > d(CGCAAATTTGCG)2 ≃ r(CGCAAAUUUGCG)2 > d(CGCATATATGCG)2 ≃ d(GACTGATCAGTC)2 > r(CGCUUUAAAGCG)2 ≃ d(CGCTTTAAAGCG)2. Compared with the mixed sequences, both r(AAAUUU) and r(UUUAAA) are greatly destablising in RNA, whereas in DNA, d(TTTAAA) is destabilising but d(AAATTT) is stabilising, which has been attributed to the formation of a special B' structure involving large propeller twists of the A-T base pairs. The solution structure of the RNA dodecamer r(CGCAAAUUUGCG)2 has been determined using NMR and restrained molecular dynamics calculations to assess the conformational reasons for its stability in comparison with d(CGCAAATTTGCG)2. The structures refined to a mean pairwise r.m.s.d. of 0.89 ± 0.29 Å. The nucleotide conformations are typical of the A family of structures. However, although the helix axis displacement is ≃ 4.6 Å into the major groove, the rise (3.0 Å) and base inclination (≃ 6°) are different from standard A form RNA. The extensive base-stacking found in the AAATTT tract of the DNA homologue that is largely responsible for the higher thermodynamic stability of the DNA duplex is reduced in the RNA structure, which may account for its low relative stability.

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