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Mechanisms of Lin28-mediated miRNA and mRNA regulation--a structural and functional perspective

Florian Mayr1, Udo Heinemann

  • 1Crystallography, Max-Delbrück Center for Molecular Medicine, Berlin 13125, Germany. florian.mayr@mdc-berlin.de

International Journal of Molecular Sciences
|August 14, 2013
PubMed

Insights

Lin28, an RNA-binding protein, regulates cell functions by controlling microRNA and mRNA. Its RNA-binding domains are key to its diverse roles in development and disease.

Area of Science:

  • Molecular Biology
  • Developmental Biology
  • Cancer Biology

Background:

  • Lin28 is a crucial RNA-binding protein in embryonic stem cells.
  • It influences differentiation, development, oncogenesis, and glucose metabolism.
  • Lin28 functions by inhibiting let-7 microRNA (miRNA) biogenesis and modulating mRNA translation.

Purpose of the Study:

  • To review recent advancements in understanding Lin28's RNA-binding mechanisms.
  • To elucidate how Lin28's structural domains contribute to its functions.
  • To explore Lin28's interaction with diverse RNA molecules.

Main Methods:

  • Biochemical and structural studies.
  • RNA crosslinking and immunoprecipitation coupled to high-throughput sequencing (CLIP-seq).

Main Results:

  • Lin28 binds to pri- and pre-let-7 miRNA, inhibiting their processing by Drosha and Dicer.
  • The Zinc-knuckle domain (ZKD) is critical for specific binding to GGAGA motifs in let-7 precursors.
  • CLIP-seq identified numerous mRNA targets, expanding the known RNA-binding landscape of Lin28.

Conclusions:

  • Lin28 utilizes its RNA-binding domains (RBDs), including the cold-shock domain (CSD) and ZKD, to regulate gene expression.
  • Structural insights reveal how Lin28 represses let-7 miRNA biogenesis.
  • Recent studies highlight Lin28's broad RNA-binding capabilities and its multifaceted roles.

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