The polyadenylation factor CstF-64 regulates alternative processing of IgM heavy chain pre-mRNA during B cell differentiation

Yoshio Takagaki, Rebecca L. Seipelt, Martha L. Peterson, James L. Manley

Research output: Contribution to journalArticlepeer-review

348 Scopus citations

Abstract

The switch from membrane-bound to secreted-form IgM that occurs during differentiation of B lymphocytes has long been known to involve regulated processing of the heavy chain pre-mRNA. Here, we show that accumulation of one subunit of an essential polyadenylation factor (CstF-64) is specifically repressed in mouse primary B cells and that overexpression of CstF-64 is sufficient to switch heavy chain expression from membrane-bound (μm) to secreted form (μs). We further show that CstF-64 is limiting for formation of intact CstF, that CstF has a higher affinity for the μm poly(A) site than for the μs site, and that the μm site is stronger in a reconstituted in vitro processing reaction. Our results indicate that CstF-64 plays a key role in regulating IgM heavy chain expression during B cell differentiation.

Original languageEnglish
Pages (from-to)941-952
Number of pages12
JournalCell
Volume87
Issue number5
DOIs
StatePublished - Nov 29 1996

Bibliographical note

Funding Information:
We thank T. Kurosaki for providing DT40 cells and pApuro vector and for helpful discussions, T. Roberts and E. C. Snow for antibodies used to purify B cells, R. Tacke for MAb104 and for helpful discussions, Y. Hirose for protein fractions containing PAP, Z. Lai and L. Ge for technical assistance, and M. Riley for preparing the manuscript. This work was supported by National Science Foundation grant MCB-9507513 to M. L. P. and National Institutes of Health grant GM28983 to J. L. M.

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology

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