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

C. Phillips, S. Jung, S. I. Gunderson

Research output: Contribution to journalArticlepeer-review

49 Scopus citations

Abstract

B-cell differentiation is accompanied by a dramatic increase in cytoplasmic accumulation and stability of the IgM heavy chain (μ) secretory mRNA. Despite considerable effort, the mechanism is unknown. We have identified three short motifs upstream of the secretory poly(A) site, which, when mutated in the g heavy chain gene, significantly increase the accumulation of the secretory form of poly(A)+ mRNA relative to the membrane form and regulate the expression of the secretory poly(A) site in a developmental manner. We 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 μ secretory mRNA. We present evidence that this mechanism is used to regulate alternative expression of other genes.

Original languageEnglish (US)
Pages (from-to)6443-6452
Number of pages10
JournalEMBO Journal
Volume20
Issue number22
DOIs
StatePublished - Nov 15 2001

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

Keywords

  • IgM heavy chain secretory mRNA
  • Novel U1A-binding motifs
  • Poly(A) addition

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