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Selective blockade of microRNA processing by Lin28

Srinivas R Viswanathan1, George Q Daley, Richard I Gregory

  • 1Stem Cell Program, Children's Hospital Boston, Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Harvard Stem Cell Institute, Boston, MA 02115, USA.

Science (New York, N.Y.)
|February 23, 2008
PubMed

Insights

Lin28 protein blocks the processing of let-7 microRNAs (miRNAs) in embryonic cells. This finding reveals Lin28 as a negative regulator of miRNA biogenesis, impacting stem cell differentiation and cancer.

Area of Science:

  • Molecular Biology
  • Developmental Biology
  • Cancer Biology

Background:

  • MicroRNAs (miRNAs) are crucial regulators of gene expression involved in development.
  • Dysregulated miRNA expression is implicated in human cancers.
  • Posttranscriptional processing of primary miRNAs (pri-miRNAs) can be inhibited in various cell types, including stem cells and tumors.

Purpose of the Study:

  • To investigate the role of Lin28, a developmental RNA-binding protein, in regulating miRNA processing.
  • To determine if Lin28 selectively affects the processing of specific pri-miRNAs.

Main Methods:

  • In vitro biochemical assays to study protein-RNA interactions.
  • In vivo studies in embryonic cells to assess the functional impact of Lin28.
  • Analysis of Microprocessor complex activity on pri-let-7 miRNAs in the presence and absence of Lin28.

Main Results:

  • Lin28 was identified as a protein that selectively blocks the processing of pri-let-7 miRNAs.
  • Lin28 was found to be both necessary and sufficient for inhibiting Microprocessor-mediated cleavage of pri-let-7 miRNAs.
  • Lin28 acts as a negative regulator of miRNA biogenesis.

Conclusions:

  • Lin28 plays a critical role in inhibiting miRNA biogenesis by blocking pri-let-7 processing.
  • Lin28 may be a key factor in preventing miRNA-mediated differentiation in stem cells.
  • The Lin28-mediated regulation of miRNA processing could be relevant to the biology of certain cancers.

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