RNA is subjected to over 100 different types of chemical modifications inside the cell. These modifications have various effects on its function and expression, resulting in RNA diversity. RNA editing or conversion of adenosine to inosine (A-to-I) in a double-stranded RNA is a type of RNA modification that can introduce mutations into the precursor of microRNA (miRNA). It can also regulate miRNA processing independently of A-to-I RNA editing. This chapter outlines the role of an A-to-I RNA editing enzyme ADAR in miRNA processing and the experimental systems used to analyze the interaction between miRNAs and ADAR.

Epstein-Barr virus (EBV) encodes BamHIA rightward transcript (BART) microRNAs (miRNAs). These miRNAs are expressed at high levels in epithelial tumors, such as nasopharyngeal carcinoma (NPC). BART miRNAs play important roles in EBV-associated malignancies, however, the reason for their high expression in NPC is unclear. We performed multiple sequence alignment of six completely sequenced EBV strains: Akata, YCCEL1, SNU719, C666-1, Mutu I, and M81. A single-nucleotide deletion was identified at the promoter region of BART. The luciferase assay suggested that this single-nucleotide polymorphism (SNP) significantly increased BART promoter activity. In addition to deletion, substitution at the same site also increased BART promoter activity. Analysis of the 170 EBV genome sequences from NPC and EBV-associated gastric cancers revealed that the frequency of this SNP was associated with NPC incidence and this SNP was found to be accumulated in the BART promoter region. Overall, our results suggested that this SNP should enhance BART promoter activity and thus, might contribute to the development of EBV-associated epithelial malignancies.