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Open Access Green as soon as Postprint is submitted to ZB.
The let-7 target gene mouse lin-41 is a stem cell specific E3 ubiquitin ligase for the miRNA pathway protein Ago2.
Nat. Cell Biol. 11, 1411-1420 (2009)
The let-7 miRNA and its target gene Lin-28 interact in a regulatory circuit controlling pluripotency. We investigated an additional let-7 target, mLin41 (mouse homologue of lin-41), as a potential contributor to this circuit. We demonstrate the presence of mLin41 protein in several stem cell niches, including the embryonic ectoderm, epidermis and male germ line. mLin41 colocalized to cytoplasmic foci with P-body markers and the miRNA pathway proteins Ago2, Mov10 and Tnrc6b. In co-precipitation assays, mLin41 interacted with Dicer and the Argonaute proteins Ago1, Ago2 and Ago4. Moreover, we show that mLin41 acts as an E3 ubiquitin ligase in an auto-ubiquitylation assay and that mLin41 mediates ubiquitylation of Ago2 in vitro and in vivo. Overexpression and depletion of mLin41 led to inverse changes in the level of Ago2 protein, implicating mLin41 in the regulation of Ago2 turnover. mLin41 interfered with silencing of target mRNAs for let-7 and miR-124, at least in part by antagonizing Ago2. Furthermore, mLin41 cooperated with the pluripotency factor Lin-28 in suppressing let-7 activity, revealing a dual control mechanism regulating let-7 in stem cells.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
caenorhabditis-elegans; posttranscriptional regulation; neuronal differentiation; RNA interference; regulatory RNA; self-renewal; ring finger; microrna; expression; brain
Language
english
Publication Year
2009
HGF-reported in Year
2009
ISSN (print) / ISBN
1465-7392
e-ISSN
1476-4679
Journal
Nature Cell Biology
Quellenangaben
Volume: 11,
Issue: 12,
Pages: 1411-1420
Publisher
Nature Publishing Group
Publishing Place
London
Reviewing status
Peer reviewed
Institute(s)
Research Unit Signaling and Translation (SAT)
POF-Topic(s)
30203 - Molecular Targets and Therapies
Research field(s)
Enabling and Novel Technologies
PSP Element(s)
G-509800-002
DOI
10.1038/ncb1987
Scopus ID
73349108109
PubMed ID
19898466
Erfassungsdatum
2009-12-31