The Epitranscriptome and Innate Immunity.

Area of Science:

• Molecular Biology
• Immunology
• Genetics

Background:

• RNA base modifications are increasingly detected across all transcript types.
• Modified bases are crucial for various RNA processes, including translation and splicing.
• Adenosine to inosine (A-to-I) RNA editing by ADAR enzymes is a well-studied modification.

Purpose of the Study:

• To explore new biological principles of RNA modifications, especially in mRNAs and long non-coding RNAs.
• To focus on the role of A-to-I RNA editing by ADAR enzymes.
• To investigate the connection between RNA modifications and innate immunity.

Main Methods:

• Review of existing literature on RNA modifications and ADAR enzymes.
• Analysis of identified A-to-I editing sites in the human transcriptome.
• Examination of recent research on epitranscriptome modifications and innate immune tolerance.

Main Results:

• Over 100 million A-to-I editing sites exist in the human transcriptome, predominantly in Alu sequences.
• Inosine in the epitranscriptome and ADAR1 protein are critical for establishing innate immune tolerance to host dsRNA.
• Innate immune sensors recognize epitranscriptome RNA modifications.

Conclusions:

• ADAR-mediated A-to-I RNA editing has significant roles beyond its known functions.
• Epitranscriptome modifications, particularly A-to-I editing, are integral to innate immune regulation.
• Further research is needed to uncover the full spectrum of RNA modification effects.