PUBLICATION

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

Authors
Wan, Y., Zhang, Q., Zhang, Z., Song, B., Wang, X., Zhang, Y., Jia, Q., Cheng, T., Zhu, X., Leung, A.Y., Yuan, W., Jia, H., Fang, X.
ID
ZDB-PUB-160311-5
Date
2016
Source
BMC Medical Genomics   9: 13 (Journal)
Registered Authors
Jia, Haibo, Leung, Anskar
Keywords
DBA, RPL5, RNA-seq, ncRNA-seq, Zebrafish
Datasets
GEO:GSE54270, GEO:GSE54152, GEO:GSE58346, GEO:GSE45699, GEO:GSE51326, GEO:GSE58344, GEO:GSE58347, GEO:GSE54259
MeSH Terms
  • Anemia, Diamond-Blackfan/genetics*
  • Animals
  • Disease Models, Animal
  • Down-Regulation/drug effects
  • Down-Regulation/genetics*
  • Embryo, Nonmammalian/metabolism
  • Gene Expression Profiling*
  • Gene Expression Regulation, Developmental/drug effects
  • Gene Regulatory Networks/drug effects
  • Hematopoiesis/drug effects
  • Hematopoiesis/genetics
  • Hemoglobins/metabolism
  • MicroRNAs/genetics
  • MicroRNAs/metabolism
  • Morpholinos/pharmacology
  • RNA, Long Noncoding/genetics
  • RNA, Long Noncoding/metabolism
  • Ribosomes/metabolism*
  • Signal Transduction/drug effects
  • Signal Transduction/genetics
  • Transcriptome/drug effects
  • Transcriptome/genetics
  • Zebrafish/genetics*
  • Zebrafish Proteins/genetics*
  • Zebrafish Proteins/metabolism
PubMed
26961822 Full text @ BMC Med. Genomics
Abstract
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.
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.
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.
Genes / Markers
Figures
Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes