Amyloid Precursor Protein mRNA Stability Is Controlled by a 29-Base Element in the 3′-Untranslated Region

Syed H E Zaidi, James S. Malter

Research output: Contribution to journalArticle

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Abstract

In the accompanying paper (Zaidi, S. H. E., Denman, R., and Malter, J. S. (1994) J. Biol. Chem. 269, 24000-24006) we demonstrate that in tumor and normal cells, multiple cytosolic proteins interact with a 29-base sequence in the 3′-untranslated region of amyloid precursor protein (APP) mRNA. These data suggested that APP gene expression may be modulated by regulated APP mRNA decay. We have investigated this prediction by measuring the decay rates of APP mRNA in resting and mitogen-treated peripheral blood mononuclear cells and H4 and K562 tumor cell lines. In resting peripheral blood mononuclear cells, APP mRNA decayed with a half-life of 4 h. Under these conditions, the activity of APP mRNA-binding proteins was not detectable. After activation, binding protein activities were induced, and APP mRNA decay was blocked with a half-life of >12 h. In log phase neuronal or lymphoid tumor cell lines, binding activity was constitutively present and APP mRNA displayed a half-life of >12 h. Protein synthesis inhibition by cycloheximide had no effect on APP mRNA decay in normal or tumor cells. Transfected wild type or mutant APP mRNAs that lacked the 29-base region were stable (t1/2 > 10 h) in K562 tumor cells. Therefore, we conclude that the 29-base region functions in cis to destabilize APP mRNA in resting, normal cells. Upon activation APP mRNA-binding proteins are induced, interact with the 29-base region, and likely participate in stabilization of the mRNA.

Original languageEnglish (US)
Pages (from-to)24007-24013
Number of pages7
JournalJournal of Biological Chemistry
Volume269
Issue number39
StatePublished - Sep 30 1994

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Amyloid beta-Protein Precursor
Protein Stability
RNA Stability
3' Untranslated Regions
Amyloid
Messenger RNA
Tumors
Half-Life
Carrier Proteins
K562 Cells
Cells
Tumor Cell Line
Protein Binding
Blood Cells
Neoplasms
Blood
Chemical activation
RNA Precursors
Mutant Proteins
Cycloheximide

ASJC Scopus subject areas

  • Biochemistry

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Amyloid Precursor Protein mRNA Stability Is Controlled by a 29-Base Element in the 3′-Untranslated Region. / Zaidi, Syed H E; Malter, James S.

In: Journal of Biological Chemistry, Vol. 269, No. 39, 30.09.1994, p. 24007-24013.

Research output: Contribution to journalArticle

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