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, 87 (5), 941-52

The Polyadenylation Factor CstF-64 Regulates Alternative Processing of IgM Heavy Chain pre-mRNA During B Cell Differentiation

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The Polyadenylation Factor CstF-64 Regulates Alternative Processing of IgM Heavy Chain pre-mRNA During B Cell Differentiation

Y Takagaki et al. Cell.

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 (microm) to secreted form (micros). We further show that CstF-64 is limiting for formation of intact CstF, that CstF has a higher affinity for the microm poly(A) site than for the micros site, and that the microm 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.

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