Blood Relatives: Splicing Mechanisms underlying Erythropoiesis in Health and Disease

F1000Research
Kirsten A Reimer, Karla M Neugebauer

Abstract

During erythropoiesis, hematopoietic stem and progenitor cells transition to erythroblasts en route to terminal differentiation into enucleated red blood cells. Transcriptome-wide changes underlie distinct morphological and functional characteristics at each cell division during this process. Many studies of gene expression have historically been carried out in erythroblasts, and the biogenesis of β-globin mRNA-the most highly expressed transcript in erythroblasts-was the focus of many seminal studies on the mechanisms of pre-mRNA splicing. We now understand that pre-mRNA splicing plays an important role in shaping the transcriptome of developing erythroblasts. Recent advances have provided insight into the role of alternative splicing and intron retention as important regulatory mechanisms of erythropoiesis. However, dysregulation of splicing during erythropoiesis is also a cause of several hematological diseases, including β-thalassemia and myelodysplastic syndromes. With a growing understanding of the role that splicing plays in these diseases, we are well poised to develop gene-editing treatments. In this review, we focus on changes in the developing erythroblast transcriptome caused by alternative splicing, the molecular b...Continue Reading

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Citations

Feb 27, 2020·Nature Communications·Ana Rio-MachinInderjeet Dokal
Aug 1, 2020·Frontiers in Genetics·Jian-Tao ZhengHong-Dong Li
Jan 14, 2021·Molecular Cell·Kirsten A ReimerKarla M Neugebauer
Aug 28, 2021·Cancers·Anna WojtuszkiewiczTorsten Haferlach

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Methods Mentioned

BETA
X-ray
dissection
MDS
RNA-seq
gene knockout
transgenic

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