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Levels of polyadenylation factor CstF-64 control IgM heavy chain mRNA accumulation and other events associated with B

Y Takagaki1, J L Manley

  • 1Department of Biological Sciences, Columbia University, New York, New York 10027, USA.

Molecular Cell
|January 14, 1999
PubMed

Insights

Cleavage stimulation factor-64 (CstF-64) regulates B cell gene expression and growth. Lowering CstF-64 levels specifically reduces IgM mRNA, impacting cell cycle and survival.

Area of Science:

  • Molecular Biology
  • Immunology
  • Cell Biology

Background:

  • Cleavage stimulation factor (CstF) is crucial for mRNA polyadenylation.
  • CstF-64 subunit concentration increases during B cell activation, influencing IgM heavy chain mRNA expression.
  • This suggests a role for CstF-64 in B cell differentiation and gene regulation.

Purpose of the Study:

  • To investigate the specific roles of CstF-64 in B cells.
  • To determine the effects of altered CstF-64 levels on IgM heavy chain mRNA accumulation and cell physiology.
  • To elucidate the broader functions of CstF-64 in B cell gene expression and growth.

Main Methods:

  • Gene disruption of endogenous CstF-64 in the DT40 B cell line.
  • Introduction of a regulatable CstF-64 transgene for controlled expression.
  • Analysis of IgM heavy chain mRNA levels, cell growth, cell cycle, and apoptosis under varying CstF-64 concentrations.

Main Results:

  • A 10-fold decrease in CstF-64 significantly reduced IgM heavy chain mRNA accumulation without affecting cell growth.
  • Further reduction in CstF-64 led to reversible cell cycle arrest in the G0/G1 phase.
  • Complete depletion of CstF-64 resulted in apoptotic cell death.

Conclusions:

  • CstF-64 plays a critical, unexpected role in regulating IgM heavy chain mRNA levels in B cells.
  • CstF-64 is essential for normal B cell growth and survival, influencing cell cycle progression.
  • These findings highlight novel functions of CstF-64 beyond its established role in mRNA polyadenylation.

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