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Csde1 binds transcripts involved in protein homeostasis and controls their expression in erythropoiesis

ABSTRACT: The RNA binding protein Csde1 (Cold shock domain protein e1) is strongly upregulated during erythropoiesis, but its expression is reduced in Diamond Blackfan Anemia (DBA). To understand the role of Csde1 in DBA, and the cellular pathways controlled by Csde1 in erythropoiesis, we identified the transcripts that physically associate with Csde1. These mainly encoded proteins involved in ribogenesis, mRNA translation and protein degradation, but also proteins associated with the mitochondrial respiratory chain and mitosis. Crispr/Cas9-mediated deletion of the first cold shock domain of Csde1 affected RNA expression and/or protein expression of Csde1-bound transcripts. Protein expression of ribogenesis factors Rpf2, Nop56 and Ebna1bp2 was reduced in the deletion mutant, while mRNA was unchanged. Protein expression of Pabpc1 was enhanced while Pabpc1 mRNA expression was reduced. Strikingly, the effect of reduced Csde1 function on mRNA stability and translation of Csde1-bound transcripts was modest. The correlation efficient between protein (iBAQ) and mRNA (RPKM) expression was not different between Csde1-bound and other transcripts. We suggest that Csde1 is involved in feed-back control in protein homeostasis and that it dampens oscillations in gene expression.

INSTRUMENT(S): Orbitrap Fusion ETD

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Blood Cell, Blood

SUBMITTER: Kat Moore

LAB HEAD: Alexander B Meijer

PROVIDER: PXD006358 | Pride | 2018-10-24

REPOSITORIES: Pride

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

Moore Kat S KS Yagci Nurcan N van Alphen Floris F Meijer Alexander B AB 't Hoen Peter A C PAC von Lindern Marieke M

PloS one 20180823 8

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 iden ...[more]

PMID: 30138317

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