Document Detail


Selective autophagy degrades DICER and AGO2 and regulates miRNA activity.
MedLine Citation:
PMID:  23143396     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
MicroRNAs (miRNAs) form a class of short RNAs (∼ 21 nucleotides) that post-transcriptionally regulate partially complementary messenger RNAs. Each miRNA may target tens to hundreds of transcripts to control key biological processes. Although the biochemical reactions underpinning miRNA biogenesis and activity are relatively well defined and the importance of their homeostasis is increasingly evident, the processes underlying regulation of the miRNA pathway in vivo are still largely elusive. Autophagy, a degradative process in which cytoplasmic material is targeted into double-membrane vacuoles, is recognized to critically contribute to cellular homeostasis. Here, we show that the miRNA-processing enzyme, DICER (also known as DICER1), and the main miRNA effector, AGO2 (also known as eukaryotic translation initiation factor 2C, 2 (EIF2C2)), are targeted for degradation as miRNA-free entities by the selective autophagy receptor NDP52 (also known as calcium binding and coiled-coil domain 2 (CALCOCO2)). Autophagy establishes a checkpoint required for continued loading of miRNA into AGO2; accordingly, NDP52 and autophagy are required for homeostasis and activity of the tested miRNAs. Autophagy also engages post-transcriptional regulation of the DICER mRNA, underscoring the importance of fine-tuned regulation of the miRNA pathway. These findings have implications for human diseases linked to misregulated autophagy, DICER- and miRNA-levels, including cancer.
Authors:
Derrick Gibbings; Serge Mostowy; Florence Jay; Yannick Schwab; Pascale Cossart; Olivier Voinnet
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Nature cell biology     Volume:  14     ISSN:  1476-4679     ISO Abbreviation:  Nat. Cell Biol.     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2013-01-17     Completed Date:  2013-01-28     Revised Date:  2013-02-06    
Medline Journal Info:
Nlm Unique ID:  100890575     Medline TA:  Nat Cell Biol     Country:  England    
Other Details:
Languages:  eng     Pagination:  1314-21     Citation Subset:  IM    
Affiliation:
Swiss Federal Institute of Technology (ETH-Z), Department of Biology, Zürich 8092, Switzerland.
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MeSH Terms
Descriptor/Qualifier:
Argonaute Proteins / genetics,  metabolism*
Autophagy / genetics,  physiology*
Cell Line
Cell Line, Tumor
HeLa Cells
Humans
Immunoprecipitation
MicroRNAs / metabolism*
Microscopy, Confocal
Microscopy, Electron
Nuclear Proteins / genetics,  metabolism
Reverse Transcriptase Polymerase Chain Reaction
Ribonuclease III / genetics,  metabolism*
Grant Support
ID/Acronym/Agency:
//Wellcome Trust
Chemical
Reg. No./Substance:
0/Argonaute Proteins; 0/EIF2C2 protein, human; 0/MicroRNAs; 0/Nuclear Proteins; 0/nuclear dot protein 52, human; EC 3.1.26.3/Ribonuclease III
Comments/Corrections
Comment In:
Nat Rev Mol Cell Biol. 2013 Jan;14(1):4-5   [PMID:  23212473 ]

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