title: A comprehensive joint analysis of the long and short RNA transcriptomes of human erythrocytes.
abstract: BACKGROUND
  Human erythrocytes are terminally differentiated, anucleate cells long thought to lack RNAs. However, previous studies have shown the persistence of many small-sized RNAs in erythrocytes. To comprehensively define the erythrocyte transcriptome, we used high-throughput sequencing to identify both short (18-24 nt) and long (>200 nt) RNAs in mature erythrocytes.
  
  
  RESULTS
  Analysis of the short RNA transcriptome with miRDeep identified 287 known and 72 putative novel microRNAs. Unexpectedly, we also uncover an extensive repertoire of long erythrocyte RNAs that encode many proteins critical for erythrocyte differentiation and function. Additionally, the erythrocyte long RNA transcriptome is significantly enriched in the erythroid progenitor transcriptome. Joint analysis of both short and long RNAs identified several loci with co-expression of both microRNAs and long RNAs spanning microRNA precursor regions. Within the miR-144/451 locus previously implicated in erythroid development, we observed unique co-expression of several primate-specific noncoding RNAs, including a lncRNA, and miR-4732-5p/-3p. We show that miR-4732-3p targets both SMAD2 and SMAD4, two critical components of the TGF-β pathway implicated in erythropoiesis. Furthermore, miR-4732-3p represses SMAD2/4-dependent TGF-β signaling, thereby promoting cell proliferation during erythroid differentiation.
  
  
  CONCLUSIONS
  Our study presents the most extensive profiling of erythrocyte RNAs to date, and describes primate-specific interactions between the key modulator miR-4732-3p and TGF-β signaling during human erythropoiesis.
authors.affiliation: Department of Molecular Genetics and Microbiology, Duke University, Durham, NC, 27710, USA. jdoss@duke.edu.|Center for Genomic and Computational Biology, Duke University, Durham, NC, 27708, USA. jdoss@duke.edu.
authors.forename: Jennifer F
authors.initials: JF
authors.lastname: Doss
authors.affiliation: Center for Genomic and Computational Biology, Duke University, Durham, NC, 27708, USA. david.corcoran@duke.edu.
authors.forename: David L
authors.initials: DL
authors.lastname: Corcoran
authors.affiliation: Center for Genomic and Computational Biology, Duke University, Durham, NC, 27708, USA. ddjima2014@gmail.com.|Department of Medicine, Duke University, Durham, NC, 27710, USA. ddjima2014@gmail.com.
authors.forename: Dereje D
authors.initials: DD
authors.lastname: Jima
authors.affiliation: Division of Hematology, Department of Medicine, and Duke Comprehensive Sickle Cell Center, Duke University, Durham, NC, 27710, USA. marilyn.telen@dm.duke.edu.
authors.forename: Marilyn J
authors.initials: MJ
authors.lastname: Telen
authors.affiliation: Center for Genomic and Computational Biology, Duke University, Durham, NC, 27708, USA. sandeep.dave@duke.edu.|Department of Medicine, Duke University, Durham, NC, 27710, USA. sandeep.dave@duke.edu.
authors.forename: Sandeep S
authors.initials: SS
authors.lastname: Dave
authors.affiliation: Department of Molecular Genetics and Microbiology, Duke University, Durham, NC, 27710, USA. jentsan.chi@duke.edu.|Center for Genomic and Computational Biology, Duke University, Durham, NC, 27708, USA. jentsan.chi@duke.edu.
authors.forename: Jen-Tsan
authors.initials: JT
authors.lastname: Chi
mesh_terms: D001483:Base Sequence; D002454:Cell Differentiation / Q000235:genetics; D004912:Erythrocytes / Q000166:cytology / Q000378:metabolism*; D020869:Gene Expression Profiling; D056426:Genetic Loci / Q000235:genetics; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D062085:RNA, Long Noncoding / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics; D051899:Smad2 Protein / Q000096:biosynthesis; D051901:Smad4 Protein / Q000096:biosynthesis; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D035683:MicroRNAs; D062085:RNA, Long Noncoding; D051899:Smad2 Protein; D051901:Smad4 Protein; D016212:Transforming Growth Factor beta