Ligands as Stabilizers of G-Quadruplexes in Non-Coding RNAs.

Joana Figueiredo,Carla Cruz,Daniela Alexandre,Jéssica Lopes-Nunes,André Miranda,Tiago Santos,Pedro Simões,Bernardo Teixeira

doi:10.3390/molecules26206164

Joana Figueiredo, Carla Cruz + Show 6 more

Open Access

https://doi.org/10.3390/molecules26206164

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Journal: Molecules (Basel, Switzerland)	Publication Date: Oct 13, 2021
Citations: 12	License type: CC BY 4.0

Affiliation: University of Beira Interior

Abstract

The non-coding RNAs (ncRNA) are RNA transcripts with different sizes, structures and biological functions that do not encode functional proteins. RNA G-quadruplexes (rG4s) have been found in small and long ncRNAs. The existence of an equilibrium between rG4 and stem−loop structures in ncRNAs and its effect on biological processes remains unexplored. For example, deviation from the stem−loop leads to deregulated mature miRNA levels, demonstrating that miRNA biogenesis can be modulated by ions or small molecules. In light of this, we report several examples of rG4s in certain types of ncRNAs, and the implications of G4 stabilization using small molecules, also known as G4 ligands, in the regulation of gene expression, miRNA biogenesis, and miRNA−mRNA interactions. Until now, different G4 ligands scaffolds were synthesized for these targets. The regulatory role of the above-mentioned rG4s in ncRNAs can be used as novel therapeutic approaches for adjusting miRNA levels.

Highlights

The ncRNAs are RNAs that are not translated into proteins and are divided into two main categories based on their size: small ncRNAs with size < 200 nt and long ncRNAs with size ≥ 200 nt [1]. ncRNAs can fold into complex structures and interact with proteins, DNA and other RNAs, modulating the activity, DNA targets, or partners of multiprotein complexes [2]
30 -untranslated regions (UTR), we report recent findings suggesting that RNA G4s (rG4) exist in the folded conformation of ncRNAs in living cells by using small molecules, termed rG4 small molecules ligands, which are able to modulate rG4 conformation (Table 1)
The bioinformatics tools showed that most of the human transcriptome is composed of ncRNAs with the widespread occurrence of potential G4-forming sequences

Summary

Introduction

The ncRNAs are RNAs that are not translated into proteins and are divided into two main categories based on their size: small ncRNAs with size < 200 nt (e.g., miRNA, piRNA, and sRNAs) and long ncRNAs with size ≥ 200 nt (e.g., lincRNA and NAT) [1]. ncRNAs can fold into complex structures and interact with proteins, DNA and other RNAs, modulating the activity, DNA targets, or partners of multiprotein complexes [2]. Of G4s according to strands polarity when polarity differences areinassociated the Conformations occurrence of bulges, the availability/nature of the central ion, the sequence flanking with an angle the G-bases and the pentose, namely. Including the number of G-quartet stacks, the length/sequence composition of the loops, the occurrence of bulges, the availability/nature of the central ion, the sequence in flanking regions, and the ligands interaction/stabilization of the rG4s [12]. Computational algorithms and next-generation sequencing (NGS), as well as the use of fluorescent light-up probes, have highlighted the location and biological as the use of fluorescent light-up probes, have highlighted the location and biological functions of rG4s in untranslated regions (UTR) of mRNA sequences [21], and more functions of rG4s in untranslated regions (UTR) of mRNA sequences [21], and more recently recently in ncRNAs [22].

Illustration

Biogenesis

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