Effect of Loops and G-Quartets on the Stability of RNA G-Quadruplexes

被引:88
作者
Pandey, Satyaprakash [1 ]
Agarwala, Prachi [1 ]
Maiti, Souvik [1 ,2 ]
机构
[1] CSIR, Inst Genom & Integrat Biol, Prote & Struct Biol Unit, Delhi 110007, India
[2] CSIR, Natl Chem Lab, Pune 411008, Maharashtra, India
关键词
HUMAN TELOMERIC RNA; REPRESSES TRANSLATION; CIRCULAR-DICHROISM; DNA; SEQUENCE; TOPOLOGY; 5-UTR; CONFORMATION; PROMOTER; APTAMER;
D O I
10.1021/jp401739m
中图分类号
O64 [物理化学(理论化学)、化学物理学];
学科分类号
070304 ; 081704 ;
摘要
The loop length, loop composition, salt concentration, and number of G-quartets are major determinants of G-quadruplex stability. We examined the effect of each of these factors on the thermal stability and folding topology of a library of RNA quadruplexes. The thermal stability of G2 and G3 RNA quadruplexes was investigated upon varying the loop length (from 1-1-1 to 15-15-15) and salt concentration (from sequence 1 to 100 mM KCl), while the effect of loop composition was explored using 18 naturally occurring potential RNA quadruplexes predicted in untranslated regions (UTRs). We found loop length and quadruplex stability to be inversely related for G2 RNA quadruplexes and G3 RNA quadruplexes with shorter loops. However, melting temperature saturates for G3 RNA quadruplexes with longer loops. RNA G-quadruplexes with longer loops (G3 15-15-15) displayed T-m values significantly higher than the physiological temperature. This study thus highlights the need to modify the consensus motif presently used by quadruplex prediction tools. An increase in the loop size from 7 bases to IS bases in the consensus motif will add to its predictive value for the discovery of potential RNA quadruplexes across transcriptomes.
引用
收藏
页码:6896 / 6905
页数:10
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