APOBEC3A cytidine deaminase induces RNA editing in monocytes and macrophages

Area of Science:

• Molecular Biology
• Genetics
• Virology

Background:

• The mechanisms and scope of RNA editing by cytidine deamination are not fully understood.
• Cytidine deaminases, particularly APOBEC3 family members, are known for their roles in DNA modification and innate immunity.

Purpose of the Study:

• To investigate the extent and enzymatic basis of C>U RNA editing in mammalian cells.
• To identify the specific enzyme responsible for RNA editing and its functional relevance.

Main Methods:

• Analysis of RNA sequencing data from macrophages and monocytes under various conditions (M1 polarization, hypoxia, interferon stimulation).
• Site-specific RNA editing analysis to identify C>U conversions.
• Enzymatic assays and mutational analysis of APOBEC3A to determine its role in RNA editing.

Main Results:

• Hundreds of gene transcripts undergo site-specific C>U RNA editing in macrophages and monocytes.
• This RNA editing alters amino acid sequences in numerous proteins, including those implicated in viral disease.
• APOBEC3A was identified as the enzyme mediating this C>U RNA editing, with key residues for DNA deamination also affecting RNA editing activity.

Conclusions:

• APOBEC3A possesses cellular RNA editing activity, acting as a C>U RNA editor.
• This study expands the known functions of APOBEC3 family proteins and advances the understanding of C>U RNA editing in mammals.
• The findings have implications for understanding viral pathogenesis and innate immune responses.