RNA editing by adenosine deaminases that act on RNA (ADARs) modifies double-stranded RNA (dsRNA) in nuclear-encoded and viral RNAs. ADARs are abundant in the nervous system and alter codons in mRNAs, fine-tuning biological pathways. They target dsRNA with little sequence specificity, converting adenosine (A) to inosine (I), which is read as guanosine (G). This process can change RNA structure and function, affecting processes like neurotransmission and splice site creation. ADARs are found in many metazoa, including mammals, birds, and worms, and their substrates include mRNAs and viral RNAs. ADARs have a conserved catalytic domain and variable dsRNA-binding motifs (dsRBMs). They are involved in modifying codons, creating splice sites, and sequestering RNA in the nucleus. ADARs also regulate gene expression by altering RNA structure and function. In mammals, ADAR1 and ADAR2 have distinct substrate preferences and are involved in viral defense. ADARs are essential for certain functions but not essential in all organisms. RNA editing in viral RNAs, such as measles and hepatitis delta viruses, is also influenced by ADARs. ADARs can create splice sites, alter RNA stability, and affect protein function. ADARs bind dsRNA with high affinity and exhibit sequence-specific preferences for certain adenosine positions. The reaction stops when the substrate becomes too single-stranded, and ADARs can bind in register to achieve uniform editing. ADARs catalyze deamination through a tetravalent intermediate, similar to other deaminases. Understanding ADARs' mechanisms and functions is crucial for elucidating their roles in RNA editing and disease.RNA editing by adenosine deaminases that act on RNA (ADARs) modifies double-stranded RNA (dsRNA) in nuclear-encoded and viral RNAs. ADARs are abundant in the nervous system and alter codons in mRNAs, fine-tuning biological pathways. They target dsRNA with little sequence specificity, converting adenosine (A) to inosine (I), which is read as guanosine (G). This process can change RNA structure and function, affecting processes like neurotransmission and splice site creation. ADARs are found in many metazoa, including mammals, birds, and worms, and their substrates include mRNAs and viral RNAs. ADARs have a conserved catalytic domain and variable dsRNA-binding motifs (dsRBMs). They are involved in modifying codons, creating splice sites, and sequestering RNA in the nucleus. ADARs also regulate gene expression by altering RNA structure and function. In mammals, ADAR1 and ADAR2 have distinct substrate preferences and are involved in viral defense. ADARs are essential for certain functions but not essential in all organisms. RNA editing in viral RNAs, such as measles and hepatitis delta viruses, is also influenced by ADARs. ADARs can create splice sites, alter RNA stability, and affect protein function. ADARs bind dsRNA with high affinity and exhibit sequence-specific preferences for certain adenosine positions. The reaction stops when the substrate becomes too single-stranded, and ADARs can bind in register to achieve uniform editing. ADARs catalyze deamination through a tetravalent intermediate, similar to other deaminases. Understanding ADARs' mechanisms and functions is crucial for elucidating their roles in RNA editing and disease.