Monomorphic RNA G-quadruplex and polymorphic DNA G-quadruplex structures responding to cellular environmental factors.

Abstract:

:We systematically and quantitatively investigated the structure and thermodynamics of G-quadruplexes of RNAs and corresponding DNAs of the same sequences under molecular crowding conditions that mimic the high osmotic stress induced by the numerous molecules inside of living cells. Structural analyses demonstrated that various telomere RNA sequences folded into parallel-stranded G-quadruplexes in a manner independent of the surrounding conditions with different cations under both dilute and molecular crowding conditions. In contrast, DNA G-quadruplexes showed structural polymorphism. Moreover, we demonstrated that the G-quadruplexes of the RNA sequences were more stable than those of the same DNA sequences. These results show that a single and robust RNA G-quadruplex structure can exist in a manner independent of the sequence and surrounding conditions. To confirm this, we studied a guanine-rich sequence located in the 5'-untranslated region of human bcl-2 mRNA that is thought to play a role in translation. The results revealed a stable parallel G-quadruplex that formed under all conditions tested. For example, a bcl-RNA G-quadruplex in the presence of 5 mM KCl [free energy change at 25 degrees C (DeltaG degrees (25)) of -5.42 kcal/mol] was more stable than its corresponding DNA G-quadruplex (DeltaG degrees (25) = -2.31 kcal/mol). Our results further indicated that water molecules binding to the 2'-OH group of RNA G-quadruplexes play a critical role in their formation and stability.

journal_name

Biochemistry

journal_title

Biochemistry

authors

Zhang DH,Fujimoto T,Saxena S,Yu HQ,Miyoshi D,Sugimoto N

doi

10.1021/bi1002822

subject

Has Abstract

pub_date

2010-06-01 00:00:00

pages

4554-63

issue

21

eissn

0006-2960

issn

1520-4995

journal_volume

49

pub_type

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