PUBLICATION

Poly(A)-specific ribonuclease mediates 3'-end trimming of Argonaute2-cleaved precursor microRNAs

Authors
Yoda, M., Cifuentes, D., Izumi, N., Sakaguchi, Y., Suzuki, T., Giraldez, A.J., Tomari, Y.
ID
ZDB-PUB-190806-5
Date
2013
Source
Cell Reports   5: 715-26 (Journal)
Registered Authors
Cifuentes, Daniel, Giraldez, Antonio, Tomari, Yukihide
Keywords
none
Datasets
GEO:GSE51036
MeSH Terms
  • Amino Acid Sequence
  • Argonaute Proteins/genetics*
  • Argonaute Proteins/metabolism
  • Exoribonucleases/metabolism*
  • Gene Expression
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • K562 Cells
  • MicroRNAs/chemistry
  • MicroRNAs/genetics
  • MicroRNAs/metabolism*
  • Molecular Sequence Data
  • Transfection
PubMed
24209750 Full text @ Cell Rep.
Abstract
MicroRNAs (miRNAs) are typically generated as ~22-nucleotide double-stranded RNAs via the processing of precursor hairpins by the ribonuclease III enzyme Dicer, after which they are loaded into Argonaute (Ago) proteins to form an RNA-induced silencing complex (RISC). However, the biogenesis of miR-451, an erythropoietic miRNA conserved in vertebrates, occurs independently of Dicer and instead requires cleavage of the 3' arm of the pre-miR-451 precursor hairpin by Ago2. The 3' end of the Ago2-cleaved pre-miR-451 intermediate is then trimmed to the mature length by an unknown nuclease. Here, using a classical chromatographic approach, we identified poly(A)-specific ribonuclease (PARN) as the enzyme responsible for the 3'-5' exonucleolytic trimming of Ago2-cleaved pre-miR-451. Surprisingly, our data show that trimming of Ago2-cleaved precursor miRNAs is not essential for target silencing, indicating that RISC is functional with miRNAs longer than the mature length. Our findings define the maturation step in the miRNA biogenesis pathway that depends on Ago2-mediated cleavage.
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Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
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Antibodies
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Mapping