Zebrafish microRNA miR-210-5p inhibits primitive myelopoiesis by silencing foxj1b and slc3a2a mRNAs downstream of gata4/5/6 transcription factor genes

Jia, W., Liang, D., Li, N., Liu, M., Dong, Z., Li, J., Dong, X., Yue, Y., Hu, P., Yao, J., Zhao, Q.
The Journal of biological chemistry   294(8): 2732-2743 (Journal)
Registered Authors
Dong, Zhangji, Hu, Ping, Liang, Dong, Yao, Jihua, Yue, Yunyun, Zhao, Qingshun
foxj1b, gata4/5/6, miR-210-5p, microRNA (miRNA), microRNA mechanism, post-transcriptional regulation, primitive myelopoiesis, slc3a2a, transcription factor, zebrafish
MeSH Terms
  • Animals
  • Embryo, Nonmammalian/cytology*
  • Embryo, Nonmammalian/metabolism
  • Forkhead Transcription Factors/antagonists & inhibitors
  • Forkhead Transcription Factors/genetics
  • Forkhead Transcription Factors/metabolism
  • Fusion Regulatory Protein 1, Heavy Chain/antagonists & inhibitors
  • Fusion Regulatory Protein 1, Heavy Chain/genetics
  • Fusion Regulatory Protein 1, Heavy Chain/metabolism
  • GATA Transcription Factors/antagonists & inhibitors
  • GATA Transcription Factors/genetics
  • GATA Transcription Factors/metabolism
  • GATA5 Transcription Factor/antagonists & inhibitors
  • GATA5 Transcription Factor/genetics
  • GATA5 Transcription Factor/metabolism
  • Gene Expression Regulation, Developmental*
  • Gene Regulatory Networks
  • Gene Silencing*
  • MicroRNAs/genetics*
  • Myelopoiesis*
  • RNA, Messenger/antagonists & inhibitors*
  • RNA, Messenger/genetics
  • RNA, Messenger/metabolism
  • Zebrafish/embryology*
  • Zebrafish/genetics
  • Zebrafish/metabolism
  • Zebrafish Proteins/antagonists & inhibitors*
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
30593510 Full text @ J. Biol. Chem.
Zebrafish gata4/5/6 genes encode transcription factors that lie on the apex of the regulatory hierarchy in primitive myelopoiesis. However, little is known about the roles of microRNAs in gata4/5/6-regulated processes. Performing RNA-Seq deep sequencing analysis of the expression changes of microRNAs in gata4/5/6-knockdown embryos, we identified miR-210-5p as a regulator of zebrafish primitive myelopoiesis. Knocking down gata4/5/6 (generating gata5/6 morphants) significantly increased miR-210-5p expression, whereas gata4/5/6 overexpression greatly reduced its expression. Consistent with inhibited primitive myelopoiesis in the gata5/6 morphants, miR-210-5p overexpression repressed primitive myelopoiesis, indicated by reduced numbers of granulocytes and macrophages. Moreover, knocking out miR-210 partially rescued the defective primitive myelopoiesis in zebrafish gata4/5/6-knockdown embryos. Furthermore, we show that the restrictive role of miR-210-5p in zebrafish primitive myelopoiesis is due to impaired differentiation of hemangioblast into myeloid progenitor cells. By comparing the set of genes with reduced expression levels in the gata5/6 morphants to the predicted target genes of miR-210-5p, we found that foxj1b and slc3a2a, encoding a forkhead box transcription factor and a solute carrier family 3 protein, respectively, are two direct downstream targets of miR-210-5p that mediate its inhibitory roles in zebrafish primitive myelopoiesis. In summary, our results reveal that miR-210-5p has an important role in the genetic network controlling zebrafish primitive myelopoiesis.
Genes / Markers
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Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Engineered Foreign Genes