She. Zaidi et Js. Malter, AMYLOID PRECURSOR PROTEIN MESSENGER-RNA STABILITY IS CONTROLLED BY A 29-BASE ELEMENT IN THE 3'-UNTRANSLATED REGION, The Journal of biological chemistry, 269(39), 1994, pp. 24007-24013
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 tum
or and normal cells, multiple cytosolic proteins interact with a 29-ba
se sequence in the 3'-untranslated region of amyloid precursor protein
(APP) mRNA. These data suggested that APP gene expression may be modu
lated by regulated APP mRNA decay. We have investigated this predictio
n by measuring the decay rates of APP mRNA in resting and mitogen-trea
ted peripheral blood mononuclear cells and H4 and K562 tumor cell line
s. In resting peripheral blood mononuclear cells, APP mRNA decayed wit
h a half-life of 4 h. Under these conditions, the activity of APP mRNA
-binding proteins was not detectable. After activation, binding protei
n 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, bin
ding activity was constitutively present and APP mRNA displayed a half
-life of >12 h. Protein synthesis inhibition by cycloheximide had no e
ffect on APP mRNA decay in normal or tumor cells. Transfected wild typ
e or mutant APP mRNAs that lacked the 29-base region were stable (t(1/
2) > 10 h) in K562 tumor cells. Therefore, we conclude that the 29-bas
e region functions in cis to destabilize APP mRNA in resting, normal c
ells. Upon activation APP mRNA-binding proteins are induced, interact
with the 29-base region, and likely participate in stabilization of th
e mRNA.