Format

Send to

Choose Destination
BMC Med Genomics. 2016 Mar 9;9:13. doi: 10.1186/s12920-016-0174-9.

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

Author information

1
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.
2
CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, 100101, China.
3
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.
4
Department of Medicine, University of Hong Kong, QMH 418, Hong Kong, China.
5
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.
6
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.
7
CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, 100101, China. fangxd@big.ac.cn.

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.

PMID:
26961822
PMCID:
PMC4785739
DOI:
10.1186/s12920-016-0174-9
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for BioMed Central Icon for PubMed Central
Loading ...
Support Center