title: Transcriptome analysis reveals a ribosome constituents disorder involved in the RPL5 downregulated zebrafish model of Diamond-Blackfan anemia.
abstract: BACKGROUND
  Diamond-Blackfan anemia (DBA) was the first ribosomopathy associated with mutations in ribosome protein (RP) genes. The clinical phenotypes of DBA include failure of erythropoiesis, congenital anomalies and cancer predisposition. Mutations in RPL5 are reported in approximately 9 ~ 21 % of DBA patients, which represents the most common pathological condition related to a large-subunit ribosomal protein. However, it remains unclear how RPL5 downregulation results in severe phenotypes of this disease.
  
  
  RESULTS
  In this study, we generated a zebrafish model of DBA with RPL5 morphants and implemented high-throughput RNA-seq and ncRNA-seq to identify key genes, lncRNAs, and miRNAs during zebrafish development and hematopoiesis. We demonstrated that RPL5 is required for both primitive and definitive hematopoiesis processes. By comparing with other DBA zebrafish models and processing functional coupling network, we identified some common regulated genes, lncRNAs and miRNAs, that might play important roles in development and hematopoiesis.
  
  
  CONCLUSIONS
  Ribosome biogenesis and translation process were affected more in RPL5 MO than in other RP MOs. Both P53 dependent (for example, cell cycle pathway) and independent pathways (such as Aminoacyl-tRNA biosynthesis pathway) play important roles in DBA pathology. Our results therefore provide a comprehensive basis for the study of molecular pathogenesis of RPL5-mediated DBA and other ribosomopathies.
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, 300020, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Wan
authors.affiliation: CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, 100101, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, 100101, China.
authors.forename: Zhaojun
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Center for Human Genome Research, Huazhong University of Science and Technology, Wuhan, Hubei, 430074, China.
authors.forename: Binfeng
authors.initials: B
authors.lastname: Song
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, 300020, China.
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, 300020, China.
authors.forename: Yingchi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Center for Human Genome Research, Huazhong University of Science and Technology, Wuhan, Hubei, 430074, China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Jia
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, 300020, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Cheng
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, 300020, China.
authors.forename: Xiaofan
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Department of Medicine, University of Hong Kong, QMH 418, Hong Kong, China.
authors.forename: Anskar Yu-Hung
authors.initials: AY
authors.lastname: Leung
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, 300020, China. wpyuan@ihcams.ac.cn.
authors.forename: Weiping
authors.initials: W
authors.lastname: Yuan
authors.affiliation: Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Center for Human Genome Research, Huazhong University of Science and Technology, Wuhan, Hubei, 430074, China. haibo.jia@hust.edu.cn.
authors.forename: Haibo
authors.initials: H
authors.lastname: Jia
authors.affiliation: CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, 100101, China. fangxd@big.ac.cn.
authors.forename: Xiangdong
authors.initials: X
authors.lastname: Fang
mesh_terms: D029503:Anemia, Diamond-Blackfan / Q000235:genetics*; D000818:Animals; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics*; D004625:Embryo, Nonmammalian / Q000378:metabolism; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D053263:Gene Regulatory Networks / Q000187:drug effects; D006410:Hematopoiesis / Q000187:drug effects / Q000235:genetics; D006454:Hemoglobins / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D060172:Morpholinos / Q000494:pharmacology; D062085:RNA, Long Noncoding / Q000235:genetics / Q000378:metabolism; D012270:Ribosomes / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D059467:Transcriptome / Q000187:drug effects / Q000235:genetics; D015027:Zebrafish / Q000235:genetics*; D029961:Zebrafish Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D006454:Hemoglobins; D035683:MicroRNAs; D060172:Morpholinos; D062085:RNA, Long Noncoding; D029961:Zebrafish Proteins