mRNA length and 3’UTR structure govern the translation selectivity in RPS14-haploinsufficient erythroblasts [transcriptome]

5q- syndrome is a somatic ribosomopathy linked to the monoallelic deletion of the RPS14 gene and characterized by a proeminent erythroid phenotype. The mechanism of anemia involves an impaired differentiation and increased apoptosis of erythroblasts. Here we show that GATA1 protein expression is low in line with a defect in the representation of its mRNA at the ribosome. A global analysis of transcripts on polysomes indicates that translation is selective with a decreased representation of the transcripts with a short coding sequence and UTRs and a highly structured 3’UTR, a subset of transcripts that includes GATA1. Our whole proteome analysis confirms that post-transcriptionally downregulated proteins were encoded by transcripts with a short length and structured 3’UTR. We identified a subset of post-translationally downregulated proteins including ribosomal proteins and translation elongation factors encoded by 5’TOP mRNAs that were enriched on the ribosome. Our results indicate that the thermodynamic characteristics of 3’UTR and in a lesser extend 5’UTR and the transcript length are the determinants of translation selectivity under RPS14 haploinsufficiency conditions and that a post-translational regulation of ribosomal proteins accounts for their decreased content in the cell. We performed transcriptome and translatome expression profiling of cells infected with shRPS14 or shSCR The purpose of the dataset is to profile analyze the effect of silencing RPS14