RNA editing in disease: mechanisms and therapeutic potential

Area of Science:

• Molecular Biology
• Genetics
• Biochemistry

Background:

• Adenosine to inosine (A-to-I) RNA editing, catalyzed by adenosine deaminases acting on RNA (ADARs), was discovered decades ago.
• The detection of A-to-I editing is facilitated by its readout as adenosine to guanosine (A-to-G) changes in cDNA sequencing, leading to widespread transcriptome analysis.
• Despite established detection methods, the functional consequences of altered RNA editing in whole transcriptome editomes and their link to disease remain poorly understood.

Purpose of the Study:

• To review the current understanding of adenosine deamination-type RNA editing.
• To explore the involvement of RNA editing in disease development.
• To discuss the potential of RNA editing as a therapeutic strategy and highlight existing challenges.

Main Methods:

• Review of existing literature on ADAR-mediated RNA editing.
• Analysis of current pipelines for detecting RNA editing events in transcriptomes.
• Discussion of the implications of RNA editing alterations in disease.

Main Results:

• A-to-I RNA editing is a prevalent post-transcriptional modification with implications for gene expression.
• Altered RNA editing patterns are increasingly linked to various human diseases, though causality is often debated.
• Site-directed RNA editing is an emerging therapeutic approach for genetic disorders, but technical hurdles persist.

Conclusions:

• Further investigation is needed to elucidate the precise role of RNA editing in disease pathogenesis.
• Exploring the dynamics of RNA editing, including single-molecule frequencies and longitudinal changes, is crucial.
• Overcoming technical challenges is essential for realizing the full therapeutic potential of RNA editing technologies.