Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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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. Examination of small RNAs (18 to 35 nucleotides) in 3 different zebrafish genotypes (wild type, MZago2, MZdicer) at 48 hours post-fertilization.

ORGANISM(S): Danio rerio

SUBMITTER: Antonio Giraldez 

PROVIDER: E-GEOD-21503 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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

Cifuentes Daniel D   Xue Huiling H   Taylor David W DW   Patnode Heather H   Mishima Yuichiro Y   Cheloufi Sihem S   Ma Enbo E   Mane Shrikant S   Hannon Gregory J GJ   Lawson Nathan D ND   Wolfe Scot A SA   Giraldez Antonio J AJ  

Science (New York, N.Y.) 20100506 5986

Dicer is a central enzyme in microRNA (miRNA) processing. We identified a Dicer-independent miRNA biogenesis pathway that uses Argonaute2 (Ago2) slicer catalytic activity. In contrast to other miRNAs, miR-451 levels were refractory to dicer loss of function but were reduced in MZago2 (maternal-zygotic) mutants. We found that pre-miR-451 processing requires Ago2 catalytic activity in vivo. MZago2 mutants showed delayed erythropoiesis that could be rescued by wild-type Ago2 or miR-451-duplex but n  ...[more]

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