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

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

SUBMITTER: van Zalen S 

PROVIDER: S-EPMC4390516 | biostudies-literature | 2015 May

REPOSITORIES: biostudies-literature