Journal Article

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

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

2008

Overview

miRNA populations, including mammalian homologues of lin-4 (mir-125) and let-7, undergo a marked transition during stem-cell differentiation 1 . 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.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: Animals / Biomedical and Life Sciences / Cancer Research / Cell Biology / Cell Differentiation / Cell division / Developmental Biology / Embryonic stem cells / Embryonic Stem Cells - cytology / Feedback, Physiological / Flow cytometry / Gene expression / Gene Expression Regulation / Gene mutations / Genetic aspects / letter / Life Sciences / Mammals / Mice / MicroRNAs / MicroRNAs - genetics / MicroRNAs - metabolism / Neurons - cytology / Neurosciences / Physiological aspects / Proteins / RNA Processing, Post-Transcriptional / RNA-Binding Proteins - genetics / RNA-Binding Proteins - metabolism / Sensors / Stem Cells