Regulatory factors governing adenosine-to-inosine (A-to-I) RNA editing

Abstract

Adenosine-to-inosine (A-to-I) RNA editing, the most prevalent mode of transcript modification in higher eukaryotes, is catalysed by the adenosine deaminases acting on RNA (ADARs). A-to-I editing imposes an additional layer of gene regulation as it dictates various aspects of RNA metabolism, including RNA folding, processing, localization and degradation. Furthermore, editing events in exonic regions contribute to proteome diversity as translational machinery decodes inosine as guanosine. Although it has been demonstrated that dysregulated A-to-I editing contributes to various diseases, the precise regulatory mechanisms governing this critical cellular process have yet to be fully elucidated. However, integration of previous studies revealed that regulation of A-to-I editing is multifaceted, weaving an intricate network of auto- and transregulations, including the involvement of virus-originated factors like adenovirus-associated RNA. Taken together, it is apparent that tipping of any regulatory components will have profound effects on A-to-I editing, which in turn contributes to both normal and aberrant physiological conditions. A complete understanding of this intricate regulatory network may ultimately be translated into new therapeutic strategies against diseases driven by perturbed RNA editing events. Herein, we review the current state of knowledge on the regulatory mechanisms governing A-to-I editing and propose the role of other co-factors that may be involved in this complex regulatory process.

LINE-associated cryptic splicing induces dsRNA-mediated interferon response and tumor immunity

“…dsRNAs are the major substrates of ADARs, which edit adenosine to inosine by deamination. 45, 46 To examine whether the predicted dsRNAs exist in cells, we analyzed ADAR-mediated editing sites on the cryptic exons with predicted dsRNA structures in control and hnRNPM KD cells. If cryptic exons form dsRNAs, they will be subjected to ADAR editing, therefore accumulating A-I editing sites.…”

ADAR Family Proteins: A Structural Review

“…Details into the networks controlling ADAR regulation are critical as ADAR RNA editing varies between tissue types, maturation, and throughout disease progression. ADAR gene expression can be altered by multiple processes specific to each ADAR member [48]. However, alterations to gene expression alone do not explain all of the complex variations in RNA editing.…”

Genome editing technologies: CRISPR, LEAPER, RESTORE, ARCUT, SATI, and RESCUE

“…Regulation in the miRNA seed region determines mRNA selection and gene silencing activity (Kume et al, 2014[ 70 ]). Moreover, this regulation allows interfering with RNA metabolism, involving the folding, processing, localization, and degradation of RNA (Hong et al, 2015[ 51 ]). Since RNA folding also affects the biology of the molecule, the folding pattern and secondary structure properties can be revealed using databases.…”