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

Mol Cell. 1998 Dec;2(6):761-71. doi: 10.1016/s1097-2765(00)80291-9.

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Apoptosis / physiology
  • B-Lymphocytes / cytology
  • B-Lymphocytes / immunology
  • B-Lymphocytes / metabolism*
  • Cell Cycle / physiology
  • Cell Differentiation / genetics
  • Cell Differentiation / immunology
  • Cell Line
  • Cell Survival / physiology
  • Chickens
  • G1 Phase
  • Gene Expression Regulation
  • Immunoglobulin Heavy Chains / genetics*
  • Immunoglobulin M / chemistry
  • Immunoglobulin M / genetics*
  • RNA, Messenger / metabolism*
  • RNA-Binding Proteins / metabolism
  • RNA-Binding Proteins / physiology*
  • Resting Phase, Cell Cycle
  • mRNA Cleavage and Polyadenylation Factors

Substances

  • Immunoglobulin Heavy Chains
  • Immunoglobulin M
  • RNA, Messenger
  • RNA-Binding Proteins
  • mRNA Cleavage and Polyadenylation Factors