Transcriptome analysis reveals a ribosome constituents disorder involved in the RPL5 downregulated zebrafish model of Diamond-Blackfan anemia View Full Text


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Article Info

DATE

2016-03-09

AUTHORS

Yang Wan, Qian Zhang, Zhaojun Zhang, Binfeng Song, Xiaomin Wang, Yingchi Zhang, Qiong Jia, Tao Cheng, Xiaofan Zhu, Anskar Yu-Hung Leung, Weiping Yuan, Haibo Jia, Xiangdong Fang

ABSTRACT

BackgroundDiamond–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.ResultsIn 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.ConclusionsRibosome 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. More... »

PAGES

13

References to SciGraph publications

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    http://scigraph.springernature.com/pub.10.1186/s12920-016-0174-9

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    http://dx.doi.org/10.1186/s12920-016-0174-9

    DIMENSIONS

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    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/26961822


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    351 grid-institutes:grid.461843.c schema:alternateName State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, 300020, Tianjin, China
    352 schema:name State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, 300020, Tianjin, China
    353 rdf:type schema:Organization
    354 grid-institutes:grid.464209.d schema:alternateName CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, 100101, Beijing, China
    355 schema:name CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, 100101, Beijing, China
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