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A novel miRNA processing pathway independent of Dicer requires Argonaute2 catalytic activity

ABSTRACT: Here we identify a Dicer-independent miRNA biogenesis pathway that employs the slicer catalytic activity of Argonaute2 (Ago2). To uncover Dicer-independent miRNAs, we sequenced small RNAs in wild type, maternal-zygotic dicer (MZdicer) and MZago2 mutants, using zebrafish as a model system. We find that, in contrast to other miRNAs, miR-451 levels were increased in MZdicer but drastically reduced in the MZago2 mutants. We show that pre-miR-451 processing requires Ago2 catalytic activity in vivo. MZago2 mutant embryos display delayed erythrocyte maturation that can be rescued by wild type Ago2 or miR-451 duplex but not catalytically dead Ago2. We propose that Ago2-mediated cleavage of a subset of pre-miRNAs, followed by uridylation and trimming, generates functional miRNAs in a Dicer-independent manner.

ORGANISM(S): Danio rerio

PROVIDER: GSE21503 | GEO | 2010/07/01

SECONDARY ACCESSION(S): PRJNA126003

REPOSITORIES: GEO

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A novel miRNA processing pathway independent of Dicer requires Argonaute2 catalytic activity

Project description:Here we identify a Dicer-independent miRNA biogenesis pathway that employs the slicer catalytic activity of Argonaute2 (Ago2). To uncover Dicer-independent miRNAs, we sequenced small RNAs in wild type, maternal-zygotic dicer (MZdicer) and MZago2 mutants, using zebrafish as a model system. We find that, in contrast to other miRNAs, miR-451 levels were increased in MZdicer but drastically reduced in the MZago2 mutants. We show that pre-miR-451 processing requires Ago2 catalytic activity in vivo. MZago2 mutant embryos display delayed erythrocyte maturation that can be rescued by wild type Ago2 or miR-451 duplex but not catalytically dead Ago2. We propose that Ago2-mediated cleavage of a subset of pre-miRNAs, followed by uridylation and trimming, generates functional miRNAs in a Dicer-independent manner. Examination of small RNAs (18 to 35 nucleotides) in 3 different zebrafish genotypes (wild type, MZago2, MZdicer) at 48 hours post-fertilization.

2010-07-01 | E-GEOD-21503 | biostudies-arrayexpress

miRNAs associated with the different human Argonaute proteins

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Project description:microRNAs (miRNAs) are typically generated as ~22-nucleotide double-stranded RNAs via processing of precursor hairpins by the RNase III enzyme Dicer, after which they are loaded into Argonaute (Ago) proteins to form RNA-induced silencing complex (RISC). However, the biogenesis of miR-451, an erythropoietic miRNA conserved in vertebrates, does not require Dicer processing. Instead, the short pre-miR-451 precursor hairpin is directly loaded into Ago, followed by cleavage of the 3' arm and trimming of the 3' end to the mature length by PARN. Here we show the in vivo activity of miR-430 Ago2-hairpin, a canonical microRNA engineered to fit the structure of miR-451 and hence become Ago2-dependent. Moreover, we test a modified miR-430 Ago2-haipin with 3x phoshorothioate bonds that impairs trimmng. Surprisingly, our data show that trimming of Ago-cleaved pre-miRNAs is not essential for target silencing, indicating that RISC is functional with miRNAs longer than 22-nucleotides. Rescue of MZdicer zebrafish mutant with the injection of trimmable and nontrimmable miR-430 Ago2 hairpins: Transcriptome of wild type, MZdicer mutant, and MZdicer mutant micoinjected with miR-430 duplex, miR-430 (Ago2-haripin), miR-430 (Ago2-haripin 3xPhosphorothioate)

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PARN mediates 3'-end trimming of Argonaute-cleaved precursor microRNAs

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