A-to-I RNA Editing in Cancer: From Evaluating the Editing Level to Exploring the Editing Effects.

Heming Wang,Yicheng Zhao,Jiayi Wei,Guangqi Song,Sinuo Chen

doi:10.3389/fonc.2020.632187

Abstract

As an important regulatory mechanism at the posttranscriptional level in metazoans, adenosine deaminase acting on RNA (ADAR)-induced A-to-I RNA editing modification of double-stranded RNA has been widely detected and reported. Editing may lead to non-synonymous amino acid mutations, RNA secondary structure alterations, pre-mRNA processing changes, and microRNA-mRNA redirection, thereby affecting multiple cellular processes and functions. In recent years, researchers have successfully developed several bioinformatics software tools and pipelines to identify RNA editing sites. However, there are still no widely accepted editing site standards due to the variety of parallel optimization and RNA high-seq protocols and programs. It is also challenging to identify RNA editing by normal protocols in tumor samples due to the high DNA mutation rate. Numerous RNA editing sites have been reported to be located in non-coding regions and can affect the biosynthesis of ncRNAs, including miRNAs and circular RNAs. Predicting the function of RNA editing sites located in non-coding regions and ncRNAs is significantly difficult. In this review, we aim to provide a better understanding of bioinformatics strategies for human cancer A-to-I RNA editing identification and briefly discuss recent advances in related areas, such as the oncogenic and tumor suppressive effects of RNA editing.

Highlights

In mammals, adenosine deaminase acting on RNA (ADAR)-induced adenine to inosine (A-to-I) is a widespread primary type of RNA editing [1]
Since inosine prefers to pair with cytidine (C), researchers have recognized A-to-I RNA editing as A-to-G editing [2]
Interpreting the level of RNA editing at the single-cell level in cancer has a great promoting effect on our further understanding of tumor heterogeneity and the development of tumor heterogeneity

Summary

Introduction

ADAR-induced adenine to inosine (A-to-I) is a widespread primary type of RNA editing [1]. ADAR proteins are able to bind to both intracellular and extranuclear double-stranded RNA (dsRNA), producing inosine (I) from adenosine (A) by deamination on RNA coding and non-coding regions. Since inosine prefers to pair with cytidine (C), researchers have recognized A-to-I RNA editing as A-to-G (guanine) editing [2]. ADAR proteins include three types in mammals, ADAR1, ADAR2 (ADARB1), and ADAR3 (ADARB2) (Figure 1A). ADAR1 and ADAR2 reside in most human tissues and are the major mediators of Ato-I RNA editing. ADAR3 is mainly expressed in the brain. ADAR1 p110 is constitutively expressed, while ADAR1 p150 is inducible

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Conclusion