Sequence divergence in the 3' untranslated regions of human zeta- and alpha-globin mRNAs mediates a difference in their stabilities and contributes to efficient alpha-to-zeta gene development switching.

Molecular and Cellular Biology
J Eric RussellS A Liebhaber

Abstract

The developmental stage-specific expression of human globin proteins is characterized by a switch from the coexpression of zeta- and alpha-globin in the embryonic yolk sac to exclusive expression of alpha-globin during fetal and adult life. Recent studies with transgenic mice demonstrate that in addition to transcriptional control elements, full developmental silencing of the human zeta-globin gene requires elements encoded within the transcribed region. In the current work, we establish that these latter elements operate posttranscriptionally by reducing the relative stability of zeta-globin mRNA. Using a transgenic mouse model system, we demonstrate that human zeta-globin mRNA is unstable in adult erythroid cells relative to the highly stable human alpha-globin mRNA. A critical determinant of the difference between alpha- and zeta-globin mRNA stability is mapped by in vivo expression studies to their respective 3' untranslated regions (3'UTRs). In vitro messenger ribonucleoprotein (mRNP) assembly assays demonstrate that the alpha- and zeta-globin 3'UTRs assemble a previously described mRNP stability-determining complex, the alpha-complex, with distinctly different affinities. The diminished efficiency of alpha-complex assembl...Continue Reading

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Citations

Dec 11, 2002·British Journal of Haematology·Onur BilenogluJ Eric Russell
Jul 28, 2007·Protein Science : a Publication of the Protein Society·Lois R ManningJames M Manning
Jul 21, 1998·Annals of the New York Academy of Sciences·S A Liebhaber, J E Russell
Jan 7, 2003·International Journal of Hematology·Hua-bing ZhangChih-Chuan Liang
Jun 8, 2000·Developmental Dynamics : an Official Publication of the American Association of Anatomists·J F ColasG C Schoenwolf
Jan 27, 2006·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Yi TangChih-chuan Liang
Jul 21, 1998·Annals of the New York Academy of Sciences·J E RussellS A Liebhaber
Mar 2, 2006·Molecular and Cellular Biology·Yong JiangJ Eric Russell
Aug 12, 1999·Biochemical and Biophysical Research Communications·R D ProkipcakC Lee
Apr 23, 2014·Journal of Hematology & Oncology·Zhenning HeJ Eric Russell
Dec 4, 2008·Molecular Therapy : the Journal of the American Society of Gene Therapy·Tamara I PestinaDerek A Persons

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