Strap associates with Csde1 and affects expression of select Csde1-bound transcripts

PLoS One. 2018 Aug 23;13(8):e0201690. doi: 10.1371/journal.pone.0201690. eCollection 2018.

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. Cold shock domain protein e1 (Csde1/Unr) 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 post-transcriptional expression control of Csde1-bound transcripts. We show that Serine/Threonine kinase receptor-associated protein (Strap/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 when associated with Csde1 is unknown. Reduced expression of Strap did not alter the pool of transcripts bound by Csde1. Instead, it altered the mRNA and/or protein expression of several Csde1-bound transcripts 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. The major cellular processes affected by both Csde1 and Strap were ribosome function and cell cycle control.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cell Cycle
  • Cell Differentiation
  • DNA-Binding Proteins / metabolism*
  • Erythroblasts / cytology
  • Erythroblasts / metabolism
  • Gene Expression Regulation*
  • Gene Knockdown Techniques
  • HEK293 Cells
  • Humans
  • Mice
  • Protein Binding
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA-Binding Proteins / metabolism*
  • Ribosomes / metabolism

Substances

  • CSDE1 protein, human
  • Carrier Proteins
  • DNA-Binding Proteins
  • RNA, Messenger
  • RNA-Binding Proteins
  • Strap protein

Grant support

This project was supported by the Landsteiner Foundation for Transfusion Research (LSBR grant 1140) and by Sanquin. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.