title: RNA splicing during terminal erythropoiesis.
abstract: OBJECTIVE
  Erythroid progenitors must accurately and efficiently splice thousands of pre-mRNAs as the cells undergo extensive changes in gene expression and cellular remodeling during terminal erythropoiesis. Alternative splicing choices are governed by interactions between RNA binding proteins and cis-regulatory binding motifs in the RNA. This review will focus on recent studies that define the genome-wide scope of splicing in erythroblasts and discuss what is known about its regulation.
  
  
  RESULTS
  RNA-seq analysis of highly purified erythroblast populations has revealed an extensive program of alternative splicing of both exons and introns. During normal erythropoiesis, stage-specific splicing transitions alter the structure and abundance of protein isoforms required for optimized red cell production. Mutation or deficiency of splicing regulators underlies hematopoietic disease in myelopdysplasia syndrome patients via disrupting the splicing program.
  
  
  CONCLUSIONS
  Erythroid progenitors execute an elaborate alternative splicing program that modulates gene expression posttranscriptionally, ultimately regulating the structure and function of the proteome in a differentiation stage-specific manner during terminal erythropoiesis. This program helps drive differentiation and ensure synthesis of the proper protein isoforms required to produce mechanically stable red cells. Mutation or deficiency of key splicing regulatory proteins disrupts the splicing program to cause disease.
authors.affiliation: Biological Systems and Engineering Division, Lawrence Berkeley National Laboratory, One Cyclotron Road, Berkeley, California, USA.
authors.forename: John G
authors.initials: JG
authors.lastname: Conboy
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D002454:Cell Differentiation / Q000235:genetics*; D015672:Erythroid Precursor Cells / Q000166:cytology* / Q000378:metabolism*; D004920:Erythropoiesis / Q000235:genetics*; D005091:Exons; D005786:Gene Expression Regulation; D006801:Humans; D007438:Introns; D009154:Mutation; D059365:Nonsense Mediated mRNA Decay; D009928:Organ Specificity / Q000235:genetics; D014176:Protein Biosynthesis; D020033:Protein Isoforms; D012326:RNA Splicing
chemical_list: D020033:Protein Isoforms