Lin28 Mediates the Terminal Uridylation of let-7 Precursor MicroRNA

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The precise control of microRNA (miRNA) biogenesis is critical for embryonic development and normal cellular functions, and its dysregulation is often associated with human diseases. Though the birth and maturation pathway of miRNA has been established, the regulation and death pathway remains largely unknown. Here, we report the RNA-binding proteins, Lin28a and Lin28b, as posttranscriptional repressors of let-7 miRNA biogenesis. We observe that the Lin28 proteins act mainly in the cytoplasm by inducing uridylation of precursor let-7 (pre-let-7) at its 3' end. The uridylated pre-let-7 (up-let-7) fails Dicer processing and undergoes degradation. We provide a mechanism for the posttranscriptional regulation of miRNA biogenesis by Lin28 which is highly expressed in undifferentiated cells and certain cancer cells. The Lin28-mediated downregulation of let-7 may play a key role in development, stem cell programming, and tumorigenesis.
Publisher
CELL PRESS
Issue Date
2008-10
Language
English
Article Type
Article
Keywords

EMBRYONIC STEM-CELLS; RNA-INTERFERENCE; CAENORHABDITIS-ELEGANS; C-ELEGANS; POSTTRANSCRIPTIONAL REGULATION; MICROPROCESSOR COMPLEX; MESSENGER-RNA; EXPRESSION; LIN-28; DICER

Citation

MOLECULAR CELL, v.32, no.2, pp.276 - 284

ISSN
1097-2765
DOI
10.1016/j.molcel.2008.09.014
URI
http://hdl.handle.net/10203/221047
Appears in Collection
MSE-Journal Papers(저널논문)
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