RNA editing of the microRNA-151 precursor blocks cleavage by the Dicer-TRBP complex.
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.
Kawahara
Yukio
Y
The Wistar Institute, 3601 Spruce Street, Philadelphia, Pennsylvania 19104, USA. ykawahara@wistar.org
Zinshteyn
Boris
B
Chendrimada
Thimmaiah P
TP
Shiekhattar
Ramin
R
Nishikura
Kazuko
K
D000243:Adenosine Deaminase / Q000235:genetics; D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000378:metabolism; D006801:Humans; D051379:Mice; D008817:Mice, Mutant Strains; D035683:MicroRNAs / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D017393:RNA Editing; D012322:RNA Precursors / Q000737:chemistry / Q000378:metabolism; D016601:RNA-Binding Proteins; D043244:Ribonuclease III / Q000737:chemistry / Q000378:metabolism*
C582434:MIRN151 microRNA, mouse; D035683:MicroRNAs; D012322:RNA Precursors; D016601:RNA-Binding Proteins; D043244:Ribonuclease III; C567955:ADARB1 protein, human; D000243:Adenosine Deaminase