title: Fas-antisense long noncoding RNA is differentially expressed during maturation of human erythrocytes and confers resistance to Fas-mediated cell death.
abstract: Long noncoding RNAs (lncRNAs) interact with other RNAs, DNA and/or proteins to regulate gene expression during development. Erythropoiesis is one developmental process that is tightly controlled throughout life to ensure accurate red blood cell production and oxygen transport to tissues. Thus, homeostasis is critical and maintained by competitive outcomes of pro- and anti-apoptotic pathways. LncRNAs are expressed during blood development; however, specific functions are largely undefined. Here, a culture model of human erythropoiesis revealed that lncRNA Fas-antisense 1 (Fas-AS1 or Saf) was induced during differentiation through the activity of essential erythroid transcription factors GATA-1 and KLF1. Saf was also negatively regulated by NF-κB, where decreasing NF-κB activity levels tracked with increasing transcription of Saf. Furthermore, Saf over-expression in erythroblasts derived from CD34(+) hematopoietic stem/progenitor cells of healthy donors reduced surface levels of Fas and conferred protection against Fas-mediated cell death signals. These studies reveal a novel lncRNA-regulated mechanism that modulates a critical cell death program during human erythropoiesis.
authors.affiliation: Department of Medical Microbiology, Immunology and Cell Biology, Southern Illinois University School of Medicine, Springfield, IL, USA.
authors.forename: Olga
authors.initials: O
authors.lastname: Villamizar
authors.affiliation: Department of Medical Microbiology, Immunology and Cell Biology, Southern Illinois University School of Medicine, Springfield, IL, USA.
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Chambers
authors.affiliation: Department of Medical Microbiology, Immunology and Cell Biology, Southern Illinois University School of Medicine, Springfield, IL, USA; Department of Pharmacology and Toxicology, Cancer Institute, University of Mississippi Medical Center, Jackson, MS, USA.
authors.forename: Yin-Yuan
authors.initials: YY
authors.lastname: Mo
authors.affiliation: Department of Medical Microbiology, Immunology and Cell Biology, Southern Illinois University School of Medicine, Springfield, IL, USA; Simmons Cancer Institute at SIU, Springfield, IL, USA.
authors.forename: Donald S
authors.initials: DS
authors.lastname: Torry
authors.affiliation: Department of Medical Microbiology, Immunology and Cell Biology, Southern Illinois University School of Medicine, Springfield, IL, USA.
authors.forename: Reese
authors.initials: R
authors.lastname: Hofstrand
authors.affiliation: Department of Hematology, St. Jude Children's Research Hospital, Memphis, TN, USA.
authors.forename: Janice M
authors.initials: JM
authors.lastname: Riberdy
authors.affiliation: Department of Hematology, St. Jude Children's Research Hospital, Memphis, TN, USA.
authors.forename: Derek A
authors.initials: DA
authors.lastname: Persons
authors.affiliation: Department of Medical Microbiology, Immunology and Cell Biology, Southern Illinois University School of Medicine, Springfield, IL, USA; Simmons Cancer Institute at SIU, Springfield, IL, USA. Electronic address: awilber@siumed.edu.
authors.forename: Andrew
authors.initials: A
authors.lastname: Wilber
mesh_terms: D017209:Apoptosis; D045744:Cell Line, Tumor; D004900:Erythroblasts / Q000166:cytology* / Q000378:metabolism; D004912:Erythrocytes / Q000166:cytology* / Q000378:metabolism; D004920:Erythropoiesis; D050982:GATA1 Transcription Factor / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D057809:HEK293 Cells; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism; D062085:RNA, Long Noncoding / Q000235:genetics*; D019014:fas Receptor / Q000235:genetics* / Q000378:metabolism
chemical_list: D050982:GATA1 Transcription Factor; D051741:Kruppel-Like Transcription Factors; D062085:RNA, Long Noncoding; C080774:erythroid Kruppel-like factor; D019014:fas Receptor; C000613269:long noncoding RNA Fas-AS1, human
keywords: Apoptosis; Erythropoiesis; Fas; Long noncoding RNA; Saf