[PDF][PDF] Levels of polyadenylation factor CstF-64 control IgM heavy chain mRNA accumulation and other events associated with B cell differentiation

Y Takagaki, JL Manley - Molecular cell, 1998 - cell.com
Y Takagaki, JL Manley
Molecular cell, 1998cell.com
Cleavage stimulation factor (CstF) is one of the multiple factors required for mRNA
polyadenylation. The concentration of one CstF subunit (CstF-64) increases during
activation of B cells, and this is sufficient to switch IgM heavy chain mRNA expression from
membrane-bound form to secreted form. To extend this observation, we disrupted the
endogenous CstF-64 gene in the B cell line DT40 and replaced it with a regulatable
transgene. Strikingly, a 10-fold decrease in CstF-64 concentration did not markedly affect …
Abstract
Cleavage stimulation factor (CstF) is one of the multiple factors required for mRNA polyadenylation. The concentration of one CstF subunit (CstF-64) increases during activation of B cells, and this is sufficient to switch IgM heavy chain mRNA expression from membrane-bound form to secreted form. To extend this observation, we disrupted the endogenous CstF-64 gene in the B cell line DT40 and replaced it with a regulatable transgene. Strikingly, a 10-fold decrease in CstF-64 concentration did not markedly affect cell growth but specifically and dramatically reduced accumulation of IgM heavy chain mRNA. Further reduction caused reversible cell cycle arrest in G0/G1 phase, while depletion resulted in apoptotic cell death. Our results indicate that CstF-64 plays unexpected roles in regulating gene expression and cell growth in B cells.
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