RNA editing of the microRNA-151 precursor blocks cleavage by the Dicer-TRBP complex

• Published in: EMBO reports Vol. 8; no. 8; pp. 763 - 769
• Main Authors: Kawahara, Yukio, Zinshteyn, Boris, Chendrimada, Thimmaiah P, Shiekhattar, Ramin, Nishikura, Kazuko
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 01.08.2007; Nature Publishing Group UK; Springer Nature B.V; Nature Publishing Group
• Subjects: ADAR; Adenosine Deaminase - genetics; Animals; Base Sequence; Brain - metabolism; Dicer; EMBO36; Genetics; Humans; Mice; Mice, Mutant Strains; microRNA; MicroRNAs - chemistry; MicroRNAs - genetics; MicroRNAs - metabolism; Molecular biology; Molecular Sequence Data; Nucleic Acid Conformation; Ribonuclease III - chemistry; Ribonuclease III - metabolism; Ribonucleic acid; RNA; RNA Editing; RNA interference; RNA Precursors - chemistry; RNA Precursors - metabolism; RNA-Binding Proteins; Scientific Report; Scientific Reports; microRNA; RNA editing; ADAR; RNA interference; Dicer
• ISSN: 1469-221X; 1469-3178; 1469-221X
• DOI: 10.1038/sj.embor.7401011

MicroRNAs (miRNAs) mediate translational repression or degradation of their target messenger RNAs by RNA interference (RNAi). The primary transcripts of miRNA genes (pri‐miRNAs) are sequentially processed by the nuclear Drosha–DGCR8 complex to approximately 60–70 nucleotide (nt) intermediates (pre‐miRNAs) and then by the cytoplasmic Dicer–TRBP complex to approximately 20–22 nt mature miRNAs. Certain pri‐miRNAs are subject to RNA editing that converts adenosine to inosine (A → I RNA editing); however, the fate of edited pri‐miRNAs is mostly unknown. Here, we provide evidence that RNA editing of pri‐miR‐151 results in complete blockage of its cleavage by Dicer and accumulation of edited pre‐miR‐151 RNAs. Our results indicate that A → I conversion at two specific positions of the pre‐miRNA foldback structure can affect its interaction with the Dicer–TRBP complex, showing a new regulatory role of A → I RNA editing in miRNA biogenesis.