Regulation of nuclear poly(A) addition controls the expression of immunoglobulin M secretory mRNA

Citation
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
Citations number
51
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Molecular Biology & Genetics
Journal title
EMBO JOURNAL
ISSN journal
0261-4189 → ACNP
Volume
20
Issue
22
Year of publication
2001
Pages
6443 - 6452
Database
ISI
SICI code
0261-4189(20011115)20:22<6443:RONPAC>2.0.ZU;2-G
Abstract
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.