Lin28 Mediates the Terminal Uridylation of let-7 Precursor MicroRNA

Mol Cell. 2008 Oct 24;32(2):276-84. doi: 10.1016/j.molcel.2008.09.014.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Cytoplasm / metabolism
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / physiology*
  • Humans
  • Mice
  • MicroRNAs / biosynthesis
  • MicroRNAs / metabolism*
  • Models, Genetic
  • RNA Precursors / metabolism*
  • RNA Processing, Post-Transcriptional
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / physiology*
  • Ribonuclease III / metabolism

Substances

  • DNA-Binding Proteins
  • LIN-28 protein, human
  • LIN28B protein, human
  • MicroRNAs
  • RNA Precursors
  • RNA-Binding Proteins
  • mirnlet7 microRNA, human
  • Ribonuclease III