A nucleolin-binding 3' untranslated region element stabilizes beta-globin mRNA in vivo

Molecular and Cellular Biology
Yong JiangJ Eric Russell

Abstract

The normal expression of human beta globin is critically dependent upon the constitutively high stability of its encoding mRNA. Unlike with alpha-globin mRNA, the specific cis-acting determinants and trans-acting factors that participate in stabilizing beta-globin mRNA are poorly described. The current work uses a linker-scanning strategy to identify a previously unknown determinant of mRNA stability within the beta-globin 3' untranslated region (3'UTR). The new determinant is positioned on an mRNA half-stem opposite a pyrimidine-rich sequence targeted by alphaCP/hnRNP-E, a factor that plays a critical role in stabilizing human alpha-globin mRNA. Mutations within the new determinant destabilize beta-globin mRNA in intact cells while also ablating its 3'UTR-specific interaction with the polyfunctional RNA-binding factor nucleolin. We speculate that 3'UTR-bound nucleolin enhances mRNA stability by optimizing alphaCP access to its functional binding site. This model is favored by in vitro evidence that alphaCP binding is enhanced both by cis-acting stem-destabilizing mutations and by the trans-acting effects of supplemental nucleolin. These studies suggest a mechanism for beta-globin mRNA stability that is related to, but distinct...Continue Reading

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Citations

Jun 26, 2009·Gene Therapy·M C Walters
Dec 4, 2008·Molecular Therapy : the Journal of the American Society of Gene Therapy·Tamara I PestinaDerek A Persons
Jun 24, 2010·The Journal of Biological Chemistry·Daniella IshimaruEleanor K Spicer
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Jun 18, 2010·Thrombosis Research·Xingge LiuJ Eric Russell

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