CA Repeats in the 3'-Untranslated Region of bcl-2 mRNA Mediate Constitutive Decay of bcl-2 mRNA

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Title
CA Repeats in the 3'-Untranslated Region of bcl-2 mRNA Mediate Constitutive Decay of bcl-2 mRNA
Author(s)
J H Lee; M H Jeon; Y J Seo; Y J Lee; Jeong Heon Ko; Y Tsujimoto; J H Lee
Bibliographic Citation
Journal of Biological Chemistry, vol. 279, no. 41, pp. 42758-42764
Publication Year
2004
Abstract
An AU-rich element (ARE) in the 3′-untranslated region (UTR) of bcl-2 mRNA has previously been shown to be responsible for destabilizing bcl-2 mRNA during apoptosis through increasing AUF1 binding. In the present study, we investigated the effect of the region upstream of the ARE on bcl-2 mRNA stability using serial deletion constructs of the 3′-UTR of bcl-2. Deletion of 30 nucleotides mostly consisting of the CA repeats, located up-stream of the ARK, resulted in the stabilization of bcl-2 mRNA abundance, in the absence or presence of the ARE. The specificity of the CA repeats in terms of destabilizing bcl-2 mRNA was proven by the substituting the CA repeats with other alternative repeats of purine/pyriminine, but this had no effect on the stability of bcl-2 mRNA. CA repeats alone, however, failed to confer instability to bcl-2 or gfp reporter mRNAs, indicating a requirement for additional sequences in the upstream region of the 3′-UTR. Serial deletion and replacement of a part of the region upstream of the CA repeats revealed that the entire 131-nucleotide upstream region is an essential prerequisite for the CA repeat-dependent destabilization of bcl-2 mRNA. Unlike the ARE, CA repeat-mediated degradation of bcl-2 mRNA was not accelerated upon apoptotic stimulus. Moreover, the upstream sequences and CA repeats are conserved among mammals. Collectively, CA repeats contribute to the constitutive decay of bcl-2 mRNA in the steady states, thereby maintaining appropriate bcl-2 levels in mammalian cells.
ISSN
0021-9258
Publisher
Amer Soc Biochemistry Molecular Biology Inc
DOI
http://dx.doi.org/10.1074/jbc.M407357200
Type
Article
Appears in Collections:
Synthetic Biology and Bioengineering Research Institute > Genome Editing Research Center > 1. Journal Articles
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