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Heterozygous mutations in the spliceosome gene<jats:italic><jats:styled-content style=\"fixed-case\">SF<\/jats:styled-content>3B1<\/jats:italic>are found in a majority of<jats:styled-content style=\"fixed-case\">RARS<\/jats:styled-content>cases. To explore the link between<jats:italic><jats:styled-content style=\"fixed-case\">SF<\/jats:styled-content>3B1<\/jats:italic>mutations and anaemia, we studied mutated<jats:styled-content style=\"fixed-case\">RARS CD<\/jats:styled-content>34<jats:sup>+<\/jats:sup>marrow cells with regard to transcriptome sequencing, splice patterns and mutational allele burden during erythroid differentiation. Transcriptome profiling during early erythroid differentiation revealed a marked up\u2010regulation of genes involved in haemoglobin synthesis and in the oxidative phosphorylation process, and down\u2010regulation of mitochondrial<jats:styled-content style=\"fixed-case\">ABC<\/jats:styled-content>transporters compared to normal bone marrow. Moreover, mis\u2010splicing of genes involved in transcription regulation, particularly haemoglobin synthesis, was confirmed, indicating a compromised haemoglobinization during<jats:styled-content style=\"fixed-case\">RARS<\/jats:styled-content>erythropoiesis. In order to define the phase during which erythroid maturation of<jats:italic><jats:styled-content style=\"fixed-case\">SF<\/jats:styled-content>3B1<\/jats:italic>mutated cells is most affected, we assessed allele burden during erythroid differentiation<jats:italic>in\u00a0vitro<\/jats:italic>and<jats:italic>in\u00a0vivo<\/jats:italic>and found that<jats:italic><jats:styled-content style=\"fixed-case\">SF<\/jats:styled-content>3B1<\/jats:italic>mutated erythroblasts showed stable expansion until late erythroblast stage but that terminal maturation to reticulocytes was significantly reduced. In conclusion,<jats:italic><jats:styled-content style=\"fixed-case\">SF<\/jats:styled-content>3B1<\/jats:italic>mutated<jats:styled-content style=\"fixed-case\">RARS<\/jats:styled-content>progenitors display impaired splicing with potential downstream consequences for genes of key importance for haemoglobin synthesis and terminal erythroid differentiation.<\/jats:p>","DOI":"10.1111\/bjh.13610","type":"journal-article","created":{"date-parts":[[2015,8,10]],"date-time":"2015-08-10T10:06:06Z","timestamp":1439201166000},"page":"478-490","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":43,"title":["Aberrant splicing of genes involved in haemoglobin synthesis and impaired terminal erythroid maturation in<i><scp>SF<\/scp>3B1<\/i>mutated refractory anaemia with ring sideroblasts"],"prefix":"10.1111","volume":"171","author":[{"given":"Simona","family":"Conte","sequence":"first","affiliation":[{"name":"Karolinska Institutet Department of 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