Two codes of RNA editing by deamination in human diseases

Area of Science:

• Molecular Biology
• Genetics
• Biochemistry

Background:

• RNA editing is a crucial post-transcriptional modification expanding biological diversity.
• Adenosine deaminases acting on RNA (ADAR) and apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like (APOBEC) enzymes mediate adenosine-to-inosine (A-to-I) and cytidine-to-uridine (C-to-U) substitutions, respectively.
• Genome-wide studies reveal widespread differential RNA editing in physiological and pathological states.

Purpose of the Study:

• To provide a comprehensive overview of ADAR-mediated A-to-I and APOBEC-mediated C-to-U RNA editing.
• To emphasize the molecular mechanisms, physiological functions, and pathological dysregulation of these two major RNA editing types.
• To highlight the implications of RNA editing in human health and disease.

Main Methods:

• Review of existing literature on RNA editing mechanisms and functions.
• Comparative analysis of ADAR and APOBEC enzymatic activities and substrates.
• Synthesis of data linking RNA editing to various diseases.

Main Results:

• RNA editing significantly contributes to transcriptomic and proteomic diversity.
• Aberrant RNA editing is implicated in immune imbalance, viral infections, neurological disorders, metabolic diseases, and cancer.
• Both A-to-I and C-to-U editing pathways offer potential for therapeutic targeting.

Conclusions:

• ADAR and APOBEC-mediated RNA editing are fundamental processes with profound impacts on cellular function.
• Dysregulation of RNA editing contributes to a wide spectrum of human diseases.
• Understanding RNA editing mechanisms is crucial for developing novel therapeutic strategies.