Transcriptome Analysis Reveals a Comprehensive Regulatory Network Involved in the Zebrafish Model of Diamond-Blackfan Anemia from RPL5 Deficiency [RNA-Seq]

In this study, we generated a zebrafish model of DBA with RPL5 morphants and implemented high-throughput RNA-seq and miRNA-seq to identify key genes, lncRNAs, and miRNAs during zebrafish development and hematopoiesis. We found that RPL5 is required for both primitive and definitive hematopoiesis processes that are partially mediated by the P53 pathway. Several genes such as cirh1a, noc2l, tars, and nol6 and miRNAs such as dre-miR-10a*, dre-miR-722, dre-miR-737, and dre-miR-142a-3p were significantly deregulated, and these changes may play a crucial role in hematopoiesis, ribosome biogenesis and development process. We also characterized the lncRNome in zebrafish with RPL5 deficiency. By constructing a comprehensive regulatory network, we identified central node genes in the network connected to the P53 pathway, almost all of which were targeted by the significantly deregulated miRNAs listed above. Our results therefore establish a regulatory network for critical genes and miRNAs involved in the RPL5-deficient zebrafish model and provide a comprehensive basis for the molecular pathogenesis of RPL5-mediated DBA and other ribosomopathies. Overall design: Determine the differences of transcriptome between RPL5-deficient and MO control zebrafish embryos for understanding the complex molecular pathogenesis of mutant RPL5-mediated human diseases

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Wan Y, Zhang Q, Zhang Z, Song B, Wang X, Zhang Y, Jia Q, Cheng T, Zhu X, Leung AY, Yuan W, Jia H, Fang X