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

805 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

Bibliographical note

Funding Information:
We are grateful to the members of our laboratory for their helpful discussion and critical reading of the manuscript. We also thank Kyung Hoon Kim and Dr. Se Won Seo for their advice on protein purification and Drs. Guhung Jung and Seung Hwan Hong for the gift of cell lines. This work was supported by the Creative Research Initiatives Program (R16-2007-073-01000-0) and the BK21 Research Fellowships (I.H., C.J., M.H., and J.H.) from the Ministry of Education, Science and Technology of Korea.

Keywords

  • PROTEINS
  • RNA

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