AUF-1 and YB-1 independently regulate β-globin mRNA in developing erythroid cells through interactions with poly(A)-binding protein. (May 2015)

• Record Type: Journal Article
• Authors: van Zalen, Sebastiaan; Lombardi, Alyssa A.; Jeschke, Grace R.; Hexner, Elizabeth O.; Russell, J. Eric
• Is Part Of: Mechanisms of development. Volume 136(2015)
• Page Start: 40
• Page End: 52
• Publication Date: 2015-05
• Subjects: Erythroid development -- β globin -- mRNA stability; Developmental biology -- Periodicals; Molecular biology -- Periodicals; Developmental Biology -- Periodicals; Molecular Biology -- Periodicals; Biologie du développement -- Périodiques; Biologie moléculaire -- Périodiques; Developmental biology; Molecular biology; Periodicals; Electronic journals; 571.8
• DOI: 10.1016/j.mod.2015.02.003
• Languages: English
• ISSNs: 0925-4773

Abstract

Highlights: AUF-1 and YB-1 assemble an mRNP β-complex on the β-globin 3′UTR. AUF-1 and YB-1 appear to serve a redundant post-transcriptional function. The β-complex enhances the binding of PABPC1 to the poly(A) tail. This mechanism may apply to nonhematopoietic AUF1- and YB1-based regulatory mRNPs. Abstract: The normal expression of β-globin protein in mature erythrocytes is critically dependent on post-transcriptional events in erythroid progenitors that ensure the high stability of β-globin mRNA. Previous work has revealed that these regulatory processes require AUF-1 and YB-1, two RNA-binding proteins that assemble an mRNP β-complex on the β-globin 3′UTR. Here, we demonstrate that the β-complex organizes during the erythropoietic interval when both β-globin mRNA and protein accumulate rapidly, implicating the importance of this regulatory mRNP to normal erythroid differentiation. Subsequent functional analyses link β-complex assembly to the half-life of β-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 β-complex assembly and β-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 β-complex assembles more efficiently on polyadenylated transcripts, implicating a model in which the β-complex enhances the binding of PABPC1 to the poly(A) tail, inhibiting mRNA deadenylation and consequently effecting the high half-life of β-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.