The polyadenylation factor CstF-64 regulates alternative processing of IgM heavy chain pre-mRNA during B cell differentiation.
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.
Takagaki
Y
Y
Department of Biological Sciences, Columbia University, New York, New York 10027, USA.
Seipelt
R L
RL
Peterson
M L
ML
Manley
J L
JL
D017398:Alternative Splicing / Q000502:physiology*; D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology* / Q000502:physiology; D002454:Cell Differentiation / Q000235:genetics; D002460:Cell Line / Q000502:physiology; D002462:Cell Membrane / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D002645:Chickens; D005786:Gene Expression Regulation / Q000235:genetics / Q000276:immunology; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007075:Immunoglobulin M / Q000737:chemistry / Q000235:genetics*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D012322:RNA Precursors / Q000737:chemistry / Q000235:genetics; D012333:RNA, Messenger / Q000502:physiology; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D011817:Rabbits; D039221:mRNA Cleavage and Polyadenylation Factors
D007143:Immunoglobulin Heavy Chains; D007075:Immunoglobulin M; D012322:RNA Precursors; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D039221:mRNA Cleavage and Polyadenylation Factors