C. Phillips et al., Regulation of nuclear poly(A) addition controls the expression of immunoglobulin M secretory mRNA, EMBO J, 20(22), 2001, pp. 6443-6452
B-cell differentiation is accompanied by a dramatic increase in cytoplasmic
accumulation and stability of the IgM heavy chain (mu) secretory mRNA. Des
pite considerable effort, the mechanism is unknown. We have identified thre
e short motifs upstream of the secretory poly(A) site, which, when mutated
in the mu heavy chain gene, significantly increase the accumulation of the
secretory form of poly(A)(+) mRNA relative to the membrane form and regulat
e the expression of the secretory poly(A) site in a developmental manner. W
e show that these motifs bind U1A and inhibit polyadenylation in vitro and
in vivo. Overexpression of U1A in vivo results in the selective inhibition
of the secretory form. Thus, this novel mechanism selectively controls post
-cleavage expression of the mu secretory mRNA. We present evidence that thi
s mechanism is used to regulate alternative expression of other genes.