Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.26.3 (RNase III)
 1,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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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PMID:Poly(A)-specific ribonuclease mediates 3'-end trimming of Argonaute2-cleaved precursor microRNAs. 2420 50

The 3' ends of metazoan microRNAs (miRNAs) are initially defined by the RNase III enzymes during maturation, but subsequently experience extensive modifications by several enzymatic activities. For example, terminal nucleotidyltransferases (TENTs) elongate miRNAs by adding one or a few nucleotides to their 3' ends, which occasionally leads to differential regulation of miRNA stability or function. However, the catalytic entities that shorten miRNAs and the molecular consequences of such shortening are less well understood, especially in vertebrates. Here, we report that poly(A)-specific ribonuclease (PARN) sculpts the 3' ends of miRNAs in human cells. By generating PARN knockout cells and characterizing their miRNAome, we demonstrate that PARN digests the 3' extensions of miRNAs that are derived from the genome or attached by TENTs, thereby effectively reducing the length of miRNAs. Surprisingly, PARN-mediated shortening has little impact on miRNA stability, suggesting that this process likely operates to finalize miRNA maturation, rather than to initiate miRNA decay. PARN-mediated shortening is pervasive across most miRNAs and appears to be a conserved mechanism contributing to the 3' end formation of vertebrate miRNAs. Our findings add miRNAs to the expanding list of noncoding RNAs whose 3' end formation depends on PARN.
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PMID:Poly(A)-specific ribonuclease sculpts the 3' ends of microRNAs. 3059 40