Cytoplasmic Poly(A) Binding Protein C4 Serves a Critical Role in Erythroid Differentiation

Abstract

The expression of an mRNA is strongly impacted by its 3′ poly(A) tail and associated poly(A)-binding proteins (PABPs). Vertebrates encode six PABP isoforms that vary in abundance, distribution, developmental control, and subcellular localization. Here we demonstrate that the minor PABP isoform PABPC4 is expressed in erythroid cells and impacts the steady-state expression of a subset of erythroid mRNAs. Motif analyses reveal a high-value AU-rich motif in the 3′ untranslated regions (UTRs) of PABPC4-impacted mRNAs. This motif enhances the association of PABPC4 with mRNAs containing critically shortened poly(A) tails. This association may serve to protect a subset of mRNAs from accelerated decay. Finally, we demonstrate that selective depletion of PABPC4 in an erythroblast cell line inhibits terminal erythroid maturation with corresponding alterations in the erythroid gene expression. These observations lead us to conclude that PABPC4 plays an essential role in posttranscriptional control of a major developmental pathway.

ACKNOWLEDGMENTS

We appreciate the generosity of laboratory members in sharing various reagents and suggestions. We acknowledge the input of the University of Pennsylvania Microarray facility for transcriptome profiling.

This work was supported by NIH MERIT HL 65449 and CA72765 award to S.A.L. H.K.K. is the recipient of a research fellowship from the Cooley's Anemia Foundation.