Abstract
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.
MeSH Terms
Adenosine Deaminase/genetics
Animals
Base Sequence
Brain/metabolism
Humans
Mice
Mice, Mutant Strains
MicroRNAs/chemistry,genetics,metabolism
Molecular Sequence Data
Nucleic Acid Conformation
RNA Editing
RNA Precursors/chemistry,metabolism
RNA-Binding Proteins
Ribonuclease III/chemistry,metabolism
Chemicals
MIRN151 microRNA, mouse
MicroRNAs
RNA Precursors
RNA-Binding Proteins
Ribonuclease III
ADARB1 protein, human
Adenosine Deaminase
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Kawahara Yukio
The Wistar Institute, 3601 Spruce Street, Philadelphia, Pennsylvania 19104, USA. ykawahara@wistar.org
Zinshteyn Boris
Chendrimada Thimmaiah P
Shiekhattar Ramin
Nishikura Kazuko
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