Csde1 cooperates with Strap to control translation of erythroid transcripts

Abstract

Erythropoiesis is regulated at many levels, including control of mRNA translation. Changing environmental conditions, such as hypoxia, or the availability of nutrients and growth factors, require a rapid response enacted by the enhanced or repressed translation of existing transcripts. Csde1 is an RNA-binding protein required for erythropoiesis and strongly upregulated in erythroblasts relative to other hematopoietic progenitors. The aim of this study is to identify the Csde1-containing protein complexes, and investigate their role in regulating the translation of Csde1-bound transcripts. We show that Strap, also called Unrip, was the protein most strongly associated with Csde1 in erythroblasts. Strap is a WD40 protein involved in signaling and RNA splicing, but its role is unknown when associated with Csde1. Reduced expression of Strap did not alter the pool of transcripts bound by Csde1. Instead, it reduced the mRNA and/or protein expression of several Csde1-bound transcript, that encode for proteins essential for translational regulation during hypoxia, such as Hmbs, eIF4g3 and Pabpc4. Also affected by Strap knockdown were Vim, a Gata-1 target crucial for erythrocyte enucleation, and Elavl1, which stabilizes Gata-1 mRNA. Thus, we found that the Csde1/Strap complex is at the crossroad of multiple pathways governing translation in erythroblasts.