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.
Publication types
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Alternative Splicing / physiology*
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Animals
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B-Lymphocytes / cytology*
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B-Lymphocytes / physiology
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Cell Differentiation / genetics
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Cell Line / physiology
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Cell Membrane / chemistry
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Cell Membrane / genetics
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Cell Membrane / metabolism
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Chickens
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Gene Expression Regulation / genetics
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Gene Expression Regulation / immunology
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Immunoglobulin Heavy Chains / genetics*
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Immunoglobulin M / chemistry
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Immunoglobulin M / genetics*
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Mice
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Mice, Inbred C3H
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Mice, Inbred C57BL
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RNA Precursors / chemistry
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RNA Precursors / genetics
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RNA, Messenger / physiology
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RNA-Binding Proteins / genetics*
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RNA-Binding Proteins / metabolism
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Rabbits
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mRNA Cleavage and Polyadenylation Factors
Substances
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Immunoglobulin Heavy Chains
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Immunoglobulin M
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RNA Precursors
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RNA, Messenger
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RNA-Binding Proteins
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mRNA Cleavage and Polyadenylation Factors