Lin28 Mediates the Terminal Uridylation of let-7 Precursor MicroRNA

Inha Heo, Chirlmin Joo, Jun Cho, Minju Ha, Jinju Han, V. Narry Kim

Research output: Contribution to journalArticlepeer-review

649 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)276-284
Number of pages9
JournalMolecular Cell
Volume32
Issue number2
DOIs
StatePublished - 24 Oct 2008

Keywords

  • PROTEINS
  • RNA

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