AUF-1 and YB-1 independently regulate ß-globin mRNA in developing erythroid cells through interactions with poly(A)-binding protein.
Mech Dev
; 136: 40-52, 2015 May.
Article
em En
| MEDLINE
| ID: mdl-25720531
ABSTRACT
The normal expression of ß-globin protein in mature erythrocytes is critically dependent on post-transcriptional events in erythroid progenitors that ensure the high stability of ß-globin mRNA. Previous work has revealed that these regulatory processes require AUF-1 and YB-1, two RNA-binding proteins that assemble an mRNP ß-complex on the ß-globin 3'UTR. Here, we demonstrate that the ß-complex organizes during the erythropoietic interval when both ß-globin mRNA and protein accumulate rapidly, implicating the importance of this regulatory mRNP to normal erythroid differentiation. Subsequent functional analyses link ß-complex assembly to the half-life of ß-globin mRNA in vivo, providing a mechanistic basis for this regulatory activity. AUF-1 and YB-1 appear to serve a redundant post-transcriptional function, as both ß-complex assembly and ß-globin mRNA levels are reduced by coordinate depletion of the two factors, and can be restored by independent rescue with either factor alone. Additional studies demonstrate that the ß-complex assembles more efficiently on polyadenylated transcripts, implicating a model in which the ß-complex enhances the binding of PABPC1 to the poly(A) tail, inhibiting mRNA deadenylation and consequently effecting the high half-life of ß-globin transcripts in erythroid progenitors. These data specify a post-transcriptional mechanism through which AUF1 and YB1 contribute to the normal development of erythropoietic cells, as well as to non-hematopoietic tissues in which AUF1- and YB1-based regulatory mRNPs have been observed to assemble on heterologous mRNAs.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteína II de Ligação a Poli(A)
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Ribonucleoproteínas Nucleares Heterogêneas Grupo D
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Células Eritroides
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Proteína 1 de Ligação a Y-Box
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Globinas beta
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article