A feedback loop comprising lin-28 and let-7 controls pre-let-7 maturation during neural stem-cell commitment View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2008-08

AUTHORS

Agnieszka Rybak, Heiko Fuchs, Lena Smirnova, Christine Brandt, Elena E Pohl, Robert Nitsch, F Gregory Wulczyn

ABSTRACT

miRNA populations, including mammalian homologues of lin-4 (mir-125) and let-7, undergo a marked transition during stem-cell differentiation. Originally identified on the basis of their mutational phenotypes in stem-cell maturation, mir-125 and let-7 are strongly induced during neural differentiation of embryonic stem (ES) cells and embryocarcinoma (EC) cells. We report that embryonic neural stem (NS) cells express let-7 and mir-125, and investigate post-transcriptional mechanisms contributing to the induction of let-7. We demonstrate that the pluripotency factor Lin-28 binds the pre-let-7 RNA and inhibits processing by the Dicer ribonuclease in ES and EC cells. In NS cells, Lin-28 is downregulated by mir-125 and let-7, allowing processing of pre-let-7 to proceed. Suppression of let-7 or mir-125 activity in NS cells led to upregulation of Lin-28 and loss of pre-let-7 processing activity, suggesting that let-7, mir-125 and lin-28 participate in an autoregulatory circuit that controls miRNA processing during NS-cell commitment. More... »

PAGES

987-993

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/ncb1759

DOI

http://dx.doi.org/10.1038/ncb1759

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1028865043

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/18604195


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