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Title: The Origins and the Biological Consequences of the Pur/Pyr DNA·RNA Asymmetry
Author: Terrazas Martínez, Montserrat
Genna, Vito
Portella, Guillem
Villegas, Núria
Sánchez, Dani
Arnan, Carme
Pulido Quetglas, Carlos
Johnson, Rory
Guigó Serra, Roderic
Brun Heath, Isabelle
Aviñó Andrés, Anna
Eritja i Casadellà, Ramon
Orozco López, Modesto
Keywords: Estereoquímica
Issue Date: 25-Apr-2019
Publisher: Elsevier Inc.
Abstract: We analyze the physical origin and the chemical and biological consequences of the asymmetry that occurs in DNA·RNA hybrids when the purine/pyrimidine (Pu/Py) ratio is different in the DNA and RNA strands. When the DNA strand of the hybrid is Py rich, the duplex is much more stable, rigid, and A-like than when the DNA strand is Pu rich. The origins of this dramatic asymmetry are double: first, the apparently innocuous substitution dT → rU produces a significant decrease in stacking, and second, backbone distortions are larger for DNA(Pu)·RNA(Py) hybrids than for the mirror RNA(Pu)·DNA(Py) ones. The functional impact of the structural and dynamic asymmetry in the biological activities of hybrids is dramatic and can be used to improve the efficiency of antisense-type strategies on the basis of the degradation of hybrids by RNase H or gene editing using CRISPR-Cas9 technology.
Note: Versió postprint del document publicat a:
It is part of: Chem, 2019, vol. 5, num. 6, p 1619-1631
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Appears in Collections:Articles publicats en revistes (Química Inorgànica i Orgànica)
Articles publicats en revistes (Institut de Recerca Biomèdica (IRB Barcelona))
Articles publicats en revistes (Bioquímica i Biomedicina Molecular)

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