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

Cell. 1996 Nov 29;87(5):941-52. doi: 10.1016/s0092-8674(00)82000-0.

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

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

MeSH terms

  • Alternative Splicing / physiology*
  • Animals
  • B-Lymphocytes / cytology*
  • B-Lymphocytes / physiology
  • Cell Differentiation / genetics
  • Cell Line / physiology
  • Cell Membrane / chemistry
  • Cell Membrane / genetics
  • Cell Membrane / metabolism
  • Chickens
  • Gene Expression Regulation / genetics
  • Gene Expression Regulation / immunology
  • Immunoglobulin Heavy Chains / genetics*
  • Immunoglobulin M / chemistry
  • Immunoglobulin M / genetics*
  • Mice
  • Mice, Inbred C3H
  • Mice, Inbred C57BL
  • RNA Precursors / chemistry
  • RNA Precursors / genetics
  • RNA, Messenger / physiology
  • RNA-Binding Proteins / genetics*
  • RNA-Binding Proteins / metabolism
  • Rabbits
  • mRNA Cleavage and Polyadenylation Factors

Substances

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