title: Muscleblind-like 1 (Mbnl1) regulates pre-mRNA alternative splicing during terminal erythropoiesis.
abstract: The scope and roles of regulated isoform gene expression during erythroid terminal development are poorly understood. We identified hundreds of differentiation-associated isoform changes during terminal erythropoiesis. Sequences surrounding cassette exons of skipped exon events are enriched for motifs bound by the Muscleblind-like (MBNL) family of splicing factors. Knockdown of Mbnl1 in cultured murine fetal liver erythroid progenitors resulted in a strong block in erythroid differentiation and disrupted the developmentally regulated exon skipping of Ndel1 mRNA, which is bound by MBNL1 and critical for erythroid terminal proliferation. These findings reveal an unanticipated scope of the alternative splicing program and the importance of Mbnl1 during erythroid terminal differentiation.
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, MA; Computational and Systems Biology Program, and.
authors.forename: Albert W
authors.initials: AW
authors.lastname: Cheng
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, MA;
authors.forename: Jiahai
authors.identifier: http://orcid.org/0000-0002-6467-8289
authors.initials: J
authors.lastname: Shi
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, MA;
authors.forename: Piu
authors.initials: P
authors.lastname: Wong
authors.affiliation: Departments of Biology and Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA; and.
authors.forename: Katherine L
authors.initials: KL
authors.lastname: Luo
authors.affiliation: Departments of Biology and Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA; and.
authors.forename: Paula
authors.initials: P
authors.lastname: Trepman
authors.affiliation: Departments of Biology and Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA; and Harvard-MIT Division of Health Sciences and Technology, Cambridge, MA.
authors.forename: Eric T
authors.initials: ET
authors.lastname: Wang
authors.affiliation: Departments of Biology and Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA; and.
authors.forename: Heejo
authors.initials: H
authors.lastname: Choi
authors.affiliation: Departments of Biology and Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA; and.
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Burge
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, MA; Departments of Biology and Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA; and.
authors.forename: Harvey F
authors.initials: HF
authors.lastname: Lodish
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D015153:Blotting, Western; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D002454:Cell Differentiation; D049109:Cell Proliferation; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D004920:Erythropoiesis / Q000502:physiology*; D005091:Exons / Q000235:genetics; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006801:Humans; D047468:Immunoprecipitation; D051379:Mice; D020033:Protein Isoforms; D012322:RNA Precursors / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D016601:RNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D002352:Carrier Proteins; D004268:DNA-Binding Proteins; C479922:Mbnl1 protein, mouse; C486015:Ndel1 protein, mouse; D020033:Protein Isoforms; D012322:RNA Precursors; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins