Regulation of Translation in Blood Stem Cells
The laboratory of Dr. Vijay Sankaran at Boston Children’s Hospital and the Broad Institute of MIT and Harvard recently reported a breakthrough discovery about the role of ribosome levels in human hematopoiesis and Diamond-Blackfan Anemia (DBA). DBA is a genetic blood disorder that is caused by mutations in genes that encode ribosomal proteins (RPs), and results in low red blood cell counts. Since RPs are broadly involved in protein translation, one of the outstanding questions was why RP gene mutations would cause reduced red blood cell counts without affecting other hematopoietic lineages. In the paper, that was published in the journal Cell ( https://doi.org/10.1016/j.cell.2018.02.036 ), Rajiv Khajuria et al. modeled loss-of-function mutations in RP genes that are found in DBA patients. They found that limited availability of ribosomes differentially affects mRNA transcripts, and especially reduces translation of transcripts with short or unstructured 5’ UTRs that are necessary ...