title: The exoribonuclease Nibbler controls 3' end processing of microRNAs in Drosophila.
abstract: MicroRNAs (miRNAs) are endogenous noncoding small RNAs with important roles in many biological pathways; their generation and activity are under precise regulation [1-3]. Emerging evidence suggests that miRNA pathways are precisely modulated with controls at the level of transcription [4-8], processing [9-11], and stability [12, 13], with miRNA deregulation linked with diseases [14] and neurodegenerative disorders [15]. In the Drosophila miRNA biogenesis pathway, long primary miRNA transcripts undergo sequential cleavage [16-18] to release the embedded miRNAs. Mature miRNAs are then loaded into Argonaute1 (Ago1) within the RNA-induced silencing complex (RISC) [19, 20]. Intriguingly, we found that Drosophila miR-34 displays multiple isoforms that differ at the 3' end, suggesting a novel biogenesis mechanism involving 3' end processing. To define the cellular factors responsible, we performed an RNA interference (RNAi) screen and identified a putative 3'→5' exoribonuclease CG9247/nibbler essential for the generation of the smaller isoforms of miR-34. Nibbler (Nbr) interacts with Ago1 and processes miR-34 within RISC. Deep sequencing analysis revealed a larger set of multi-isoform miRNAs that are controlled by nibbler. These findings suggest that Nbr-mediated 3' end processing represents a critical step in miRNA maturation that impacts miRNA diversity.
authors: Department of Biology, University of Pennsylvania and University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
authors: Nan
authors: N
authors: Liu
authors: Masashi
authors: M
authors: Abe
authors: Leah R
authors: LR
authors: Sabin
authors: Gert-Jan
authors: GJ
authors: Hendriks
authors: Ammar S
authors: AS
authors: Naqvi
authors: Zhenming
authors: Z
authors: Yu
authors: Sara
authors: S
authors: Cherry
authors: Nancy M
authors: NM
authors: Bonini
mesh_terms: D000818:Animals; D060565:Argonaute Proteins / Q000235:genetics / Q000378:metabolism; D015152:Blotting, Northern; D002460:Cell Line; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000235:genetics / Q000378:metabolism*; D005095:Exoribonucleases / Q000378:metabolism*; D035683:MicroRNAs / Q000378:metabolism*; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D034622:RNA Interference; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000378:metabolism; D034743:RNA-Induced Silencing Complex / Q000378:metabolism; D017423:Sequence Analysis, RNA
chemical_list: C489654:AGO1 protein, Drosophila; D060565:Argonaute Proteins; D029721:Drosophila Proteins; C570893:MIRN34 microRNA, Drosophila; D035683:MicroRNAs; D012333:RNA, Messenger; D034743:RNA-Induced Silencing Complex; D005095:Exoribonucleases; C570892:Nbr protein, Drosophila