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Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
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.
Impact Factor
Scopus SNIP
Web of Science
Times Cited
Times Cited
Scopus
Cited By
Cited By
Altmetric
17.774
3.550
114
176
Anmerkungen
Besondere Publikation
Auf Hompepage verbergern
Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Schlagwörter
caenorhabditis-elegans; posttranscriptional regulation; neuronal differentiation; RNA interference; regulatory RNA; self-renewal; ring finger; microrna; expression; brain
Sprache
englisch
Veröffentlichungsjahr
2009
HGF-Berichtsjahr
2009
ISSN (print) / ISBN
1465-7392
e-ISSN
1476-4679
Zeitschrift
Nature Cell Biology
Quellenangaben
Band: 11,
Heft: 12,
Seiten: 1411-1420
Verlag
Nature Publishing Group
Verlagsort
London
Begutachtungsstatus
Peer reviewed
Institut(e)
Research Unit Signaling and Translation (SAT)
POF Topic(s)
30203 - Molecular Targets and Therapies
Forschungsfeld(er)
Enabling and Novel Technologies
PSP-Element(e)
G-509800-002
DOI
10.1038/ncb1987
Scopus ID
73349108109
PubMed ID
19898466
Erfassungsdatum
2009-12-31