Letter abstract
Nature Cell Biology
Published online: 6 July 2008 | doi:10.1038/ncb1759
A feedback loop comprising lin-28 and let-7 controls pre-let-7 maturation during neural stem-cell commitment
Agnieszka Rybak1,2, Heiko Fuchs1,2, Lena Smirnova1, Christine Brandt1, Elena E. Pohl1, Robert Nitsch1 & F. Gregory Wulczyn1
miRNA populations, including mammalian homologues of lin-4 (mir-125) and let-7, undergo a marked transition during stem-cell differentiation1. 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.
- Institute of Cell and Neurobiology, Center for Anatomy, Charité – Universitätsmedizin Berlin, Berlin, Germany.
- These authors contributed equally to this work.
Correspondence to: F. Gregory Wulczyn1 e-mail: gregory.wulczyn@charite.de