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Biochim Biophys Acta. 2014 Dec;1840(12):3503-10. doi: 10.1016/j.bbagen.2014.08.017. Epub 2014 Sep 16.

Role of G-quadruplex located at 5' end of mRNAs.

Author information

1
Proteomics and Structural Biology Unit, CSIR-Institute of Genomics and Integrative Biology, Mall Road, Delhi 110007, India; Academy of Scientific and Innovative Research (AcSIR), Anusandhan Bhawan, 2 Rafi Marg, New Delhi 110001, India.
2
Proteomics and Structural Biology Unit, CSIR-Institute of Genomics and Integrative Biology, Mall Road, Delhi 110007, India; Academy of Scientific and Innovative Research (AcSIR), Anusandhan Bhawan, 2 Rafi Marg, New Delhi 110001, India; CSIR-National Chemical Laboratory, Dr. Homi Bhabha Road, Pune 411008, India. Electronic address: souvik@igib.res.in.

Abstract

BACKGROUND:

Secondary structures in 5' UTR of mRNAs play a critical role in regulating protein synthesis. Though studies have indicated the role of secondary structure G-quadruplex in translational regulation, position-specific effect of G-quadruplex in naturally occurring mRNAs is still not understood. As a pre-initiation complex recognises 5' cap of the mRNA and scans along the untranslated region (UTR) before initiating translation, the presence of G-quadruplex in 5' region may have a significant contribution in regulating translation. Here, we investigate the role of G-quadruplex located at the 5' end of an mRNA.

METHODS:

Biophysical characterisation of putative G-quadruplexes was performed using UV and CD spectroscopy. Functional implication of G-quadruplex in the context of their location was assessed in cellulo using qRT-PCR and dual luciferase assay system.

RESULTS:

PG4 sequences in 5' UTR of AKT interacting protein (AKTIP), cathepsin B (CTSB) and forkhead box E3 (FOXE3) mRNAs form G-quadruplex whereas it is unable to form G-quadruplex in apolipoprotein A-I binding protein (APOA1BP). Our results demonstrated diverse roles of G-quadruplex located at 5' end of mRNAs. Though G-quadruplex in AKTIP and CTSB mRNA act as inhibitory modules, it activates translation in FOXE3 mRNA.

CONCLUSIONS:

Our works suggests that G-quadruplex present at the 5' terminal of an mRNA behaves differently in a different gene context. It can activate or inhibit gene expression.

GENERAL SIGNIFICANCE:

This study demonstrated that it is difficult to predict the role of G-quadruplex on the basis of its position in 5' UTR. The neighbouring nucleotide sequence, the intracellular milieu and the interacting partners might render diverse functions to this secondary structure.

KEYWORDS:

AKTIP; APOA1BP; CTSB; FOXE3; G-quadruplex; UTR

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