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Ribosome profiling of human platelets, reticulocytes, and in vitro cell lines

ABSTRACT: Translation is a fundamental biological process and ribosomes are essential in all cells, but defects in ribosome biogenesis (ribosomopathies) disproportionately cause hematopoietic dysfunction of red blood cells and platelets. Here, we analyze translation in primary human reticulocytes and platelets by ribosome profiling and uncover dramatic accumulation of post-termination, unrecycled ribosomes in the 3´UTRs of mRNAs. We then demonstrate that these ribosomes accumulate as a result of the natural loss of the ribosome recycling factor ABCE1 during terminal differentiation. We find that induction of ribosome rescue factors PELO and HBS1L is required to maintain translational homeostasis when ABCE1 levels fall. This activation of ribosome rescue mitigates the effects of ribosome shortage on translational output, including on hemoglobin production. Our observations suggest that this distinctive loss of ABCE1 in anucleate blood lineages sensitizes them to defects in ribosome homeostasis and that activation of a ribosome rescue pathway plays a lineage-specific role in maintaining ribosome homeostasis during blood cell development.

ORGANISM(S): Homo sapiens

PROVIDER: GSE85864 | GEO | 2016/09/29

SECONDARY ACCESSION(S): PRJNA339577

REPOSITORIES: GEO

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