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Regulated globin mRNA decay is a cytoplasmic event proceeding through 3′-to-5′ exosome-dependent decapping

Published online by Cambridge University Press:  16 January 2003

NANCY D. RODGERS
Affiliation:
Department of Cell Biology and Neuroscience, Rutgers University, Piscataway, New Jersey 08854-8082, USA
ZUOREN WANG
Affiliation:
Department of Cell Biology and Neuroscience, Rutgers University, Piscataway, New Jersey 08854-8082, USA
MEGERDITCH KILEDJIAN
Affiliation:
Department of Cell Biology and Neuroscience, Rutgers University, Piscataway, New Jersey 08854-8082, USA
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Abstract

The α-globin mRNA contains a C-rich stability element (CRE) in its 3′ untranslated region (3′ UTR) which is critical for the stability of this long-lived mRNA. A protein complex, termed the α-complex, forms on the CRE and has been shown to contribute to stabilization of the mRNA by at least two mechanisms, first by interacting with the poly(A)-binding protein (PABP) to prevent deadenylation, and second by protecting the mRNA from attack by an erythroid endoribonuclease. In this report, we demonstrate that the α-globin 3′ UTR can confer stability on a heterologous mRNA in cells, and this stability is dependent on the α-complex. Moreover, the stability was exclusively detected with cytoplasmic mRNA, suggesting that the regulation of α-globin mRNA stability is a cytoplasmic event. An additional mechanism by which the α-complex can confer stability on an RNA in vitro was also identified and shown to involve inhibition of 3′ to 5′ exonucleolytic degradation. Furthermore, using an in vitro mRNA decay system, we were able to follow the demise of the α-globin RNA and demonstrate that the decay was initiated by deadenylation followed by 3′-to-5′ decay carried out by the exosome and ultimately hydrolysis of the residual cap structure.

Type
Research Article
Information
RNA , Volume 8 , Issue 12 , December 2002 , pp. 1526 - 1537
Copyright
2002 RNA Society

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Regulated globin mRNA decay is a cytoplasmic event proceeding through 3′-to-5′ exosome-dependent decapping
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