title: The Poly(C) Binding Protein Pcbp2 and Its Retrotransposed Derivative Pcbp1 Are Independently Essential to Mouse Development.
abstract: RNA-binding proteins participate in a complex array of posttranscriptional controls essential to cell type specification and somatic development. Despite their detailed biochemical characterizations, the degree to which each RNA-binding protein impacts mammalian embryonic development remains incompletely defined, and the level of functional redundancy among subsets of these proteins remains open to question. The poly(C) binding proteins, PCBPs (αCPs and hnRNP E proteins), are encoded by a highly conserved and broadly expressed gene family. The two major Pcbp isoforms, Pcbp2 and Pcbp1, are robustly expressed in a wide range of tissues and exert both nuclear and cytoplasmic controls over gene expression. Here, we report that Pcbp1-null embryos are rendered nonviable in the peri-implantation stage. In contrast, Pcbp2-null embryos undergo normal development until midgestation (12.5 to 13.5 days postcoitum), at which time they undergo a dramatic loss in viability associated with combined cardiovascular and hematopoietic abnormalities. Mice heterozygous for either Pcbp1 or Pcbp2 null alleles display a mild and nondisruptive defect in initial postpartum weight gain. These data reveal that Pcbp1 and Pcbp2 are individually essential for mouse embryonic development and have distinct impacts on embryonic viability and that Pcpb2 has a nonredundant in vivo role in hematopoiesis. These data further provide direct evidence that Pcbp1, a retrotransposed derivative of Pcpb2, has evolved an essential function(s) in the mammalian genome.
authors.affiliation: Gastroenterology, Hepatology and Nutrition Division, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA Department of Genetics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Louis R
authors.initials: LR
authors.lastname: Ghanem
authors.affiliation: Department of Genetics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Kromer
authors.affiliation: Department of Genetics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Ian M
authors.initials: IM
authors.lastname: Silverman
authors.affiliation: Department of Genetics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Priya
authors.initials: P
authors.lastname: Chatterji
authors.affiliation: Cell and Molecular Biology Graduate Group, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Traxler
authors.affiliation: Gastroenterology Division, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Penzo-Mendez
authors.affiliation: Department of Hematology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
authors.forename: Mitchell J
authors.initials: MJ
authors.lastname: Weiss
authors.affiliation: Gastroenterology Division, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Ben Z
authors.initials: BZ
authors.lastname: Stanger
authors.affiliation: Department of Genetics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA Division of Hematology and Oncology, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA liebhabe@mail.med.upenn.edu.
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Liebhaber
mesh_terms: D000818:Animals; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D004268:DNA-Binding Proteins; D004622:Embryo, Mammalian / Q000378:metabolism; D017353:Gene Deletion; D005786:Gene Expression Regulation; D056426:Genetic Loci; D006410:Hematopoiesis; D051379:Mice / Q000196:embryology* / Q000235:genetics; D008969:Molecular Sequence Data; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D059467:Transcriptome
chemical_list: D002352:Carrier Proteins; D004268:DNA-Binding Proteins; C121375:Pcbp1 protein, mouse; C501904:Pcbp2 protein, mouse; D016601:RNA-Binding Proteins