Combinatorial role of two G-quadruplexes in 5' UTR of transforming growth factor β2 (TGFβ2).

Albeit most studies demonstrate the inhibitory role of G-quadruplex in the 5' Untranslated Region (5' UTR), our previous report depicted its completely contrasting activating role in the 5' UTR of transforming growth factor β2 (TGFβ2) mRNA. Therefore, we screened the 5' UTR of TGFβ2 manually and identified a second putative G-quadruplex sequence. Our in vitro experiments encompassing CD and UV spectroscopy confirmed the ability of this sequence to form a G-quadruplex and in cellulo studies further indicated its activating role in modulation of TGFβ2 gene expression.

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

The classic G-quadruplex motif consists of a continuous array of 3-4 guanine residues with an intermittent loop size of 1-7 nucleotides (GNGNGNG). 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.

The RNA Stem-Loop to G-Quadruplex Equilibrium Controls Mature MicroRNA Production inside the Cell.

The biological role of the existence of overlapping structures in RNA is possible yet remains very unexplored. G-Rich tracts of RNA form G-quadruplexes, while GC-rich sequences prefer stem-loop structures. The equilibrium between alternate structures within RNA may occur and influence its functionality.

The tale of RNA G-quadruplex.

G-quadruplexes are non-canonical secondary structures found in guanine rich regions of DNA and RNA. Reports have indicated the wide occurrence of RNA G-quadruplexes across the transcriptome in various regions of mRNAs and non-coding RNAs. RNA G-quadruplexes have been implicated in playing an important role in translational regulation, mRNA processing events and maintenance of chromosomal end integrity.

Human telomeric RNA G-quadruplex response to point mutation in the G-quartets.

Many putative G-quadruplex forming sequences have been predicted to exist in the human genome and transcriptome. As these sequences are subject to point mutations or SNPs (single nucleotide polymorphisms) during the course of evolution, we attempt to understand impact of these mutations in context of RNA G-quadruplex formation using human telomeric RNA (TERRA) as a model sequence. Our studies suggest that G-quadruplex stability is sensitive to substitution of the guanines comprising G-quartets.

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

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.

G-quadruplexes as tools for synthetic biology.

With the potential to engineer biological systems, synthetic biology is an emerging field that combines various disciplines of sciences. It encompasses combinations of DNA, RNA and protein modules for constructing desired systems and the "rewiring" of existing signalling networks. Despite recent advances, this field still lags behind in the artificial reconstruction of cellular processes, and thus demands new modules and switches to create "genetic circuits".

Effect of loops and G-quartets on the stability of RNA G-quadruplexes.

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 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).

The G-quadruplex augments translation in the 5' untranslated region of transforming growth factor β2.

Transforming growth factor β2 (TGFβ2) is a versatile cytokine with a prominent role in cell migration, invasion, cellular development, and immunomodulation. TGFβ2 promotes the malignancy of tumors by inducing epithelial-mesenchymal transition, angiogenesis, and immunosuppression. As it is well-documented that nucleic acid secondary structure can regulate gene expression, we assessed whether any secondary motif regulates its expression at the post-transcriptional level.

RNA G-quadruplexes: G-quadruplexes with "U" turns.

G-quadruplexes are non canonical secondary structures held together by Hoogsteen bonded planar guanine quartets formed in G-rich sequences in DNA and RNA. Considerable research over the past three decades has contributed to a great deal of understanding of these unusual structures in DNA. Various factors governing the stability of DNA quadruplexes coupled with their in vivo existence have been well documented.