Mutagenesis Reveals an Unusual Combination of Guanines in RNA G-Quadruplex Formation

Prachi Agarwala; Gargi Pal; Satyaprakash Pandey; Souvik Maiti

doi:10.1021/acsomega.7b00377

Mutagenesis Reveals an Unusual Combination of Guanines in RNA G-Quadruplex Formation

ACS Omega. 2017 Aug 22;2(8):4790-4799. doi: 10.1021/acsomega.7b00377. eCollection 2017 Aug 31.

Authors

Prachi Agarwala^{1

2}, Gargi Pal², Satyaprakash Pandey^{1

2}, Souvik Maiti^{1

2}

Affiliations

¹ Chemical and Systems Biology, CSIR-Institute of Genomics and Integrative Biology, Mall Road, Delhi 110007, India.
² Academy of Scientific and Innovative Research (AcSIR), Anusandhan Bhawan, 2 Rafi Marg, New Delhi 110001, India.

Abstract

The classic G-quadruplex motif consists of a continuous array of 3-4 guanine residues with an intermittent loop size of 1-7 nucleotides (G_3-4N_1-7G_3-4N_1-7G_3-4N_1-7G_3-4). An RNA G-quadruplex is able to attain only one parallel G-quadruplex topology owing to steric constraints. Investigating the possibilities of the formation of RNA G-quadruplexes with a stretch of sequences deviating from this classic motif will add to the overall conformations of RNA G-quadruplexes, bestowing diversity to this structure. Here, we report unusual combinations of guanine residues involved in RNA G-quadruplex formation in the 5' untranslated region (UTR) of the von Willebrand factor (VWF) mRNA using the mutagenesis approach. Different permutations and combinations of guanine residues form G-quadruplexes. Upon investigation, G-quadruplexes in 5' UTR of VWF mRNA are shown to exhibit an inhibitory function.