Detecting and Profiling Endogenous RNA G-Quadruplexes in the Human Transcriptome.

Xiao Sun,Yue Hou,Yajun Liu,Rongxin Zhang,Xingxing Zhang,Ke Xiao,Hongde Liu

doi:10.3390/ijms22158012

Abstract

G-quadruplexes are the non-canonical nucleic acid structures that are preferentially formed in G-rich regions. This structure has been shown to be associated with many biological functions. Regardless of the broad efforts on DNA G-quadruplexes, we still have limited knowledge on RNA G-quadruplexes, especially in a transcriptome-wide manner. Herein, by integrating the DMS-seq and the bioinformatics pipeline, we profiled and depicted the RNA G-quadruplexes in the human transcriptome. The genes that contain RNA G-quadruplexes in their specific regions are significantly related to immune pathways and the COVID-19-related gene sets. Bioinformatics analysis reveals the potential regulatory functions of G-quadruplexes on miRNA targeting at the scale of the whole transcriptome. In addition, the G-quadruplexes are depleted in the putative, not the real, PAS-strong poly(A) sites, which may weaken the possibility of such sites being the real cleaved sites. In brief, our study provides insight into the potential function of RNA G-quadruplexes in post-transcription.

Highlights

G-quadruplexes are the non-canonical nucleic acid secondary structures that are formed by stacking G-quartets on top of each other
Computational methods have identified more than 350,000 DNA G-quadruplex-forming sequences in the human genome, which are usually located in some important genomic regions, such as promoters and telomeres, indicating that Gquadruplexes are involved in many critical biological processes [2]
We focused on the canonical RNA G-quadruplexes (GxN1−7GxN1−7GxN1−7Gx, where x ≥ 3 and N can be any base)

Summary

Introduction

G-quadruplexes are the non-canonical nucleic acid secondary structures that are formed by stacking G-quartets on top of each other. Each G-quartet planar comprises four guanines, where adjacent guanines are bonded to each other via Hoogsteen hydrogen [1]. The stability of G-quadruplexes is partially determined by monovalent cations which are located within or between the plane of G-quartets. G-quadruplexes can adopt parallel, antiparallel or hybrid structures, which mainly depend on the orientation of the strands. The number and orientation of the strands highlight the diversity of G-quadruplex structure topologies [1]. Computational methods have identified more than 350,000 DNA G-quadruplex-forming sequences in the human genome, which are usually located in some important genomic regions, such as promoters and telomeres, indicating that Gquadruplexes are involved in many critical biological processes [2]

Methods

Results

Conclusion