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

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.