ZFIN ID: ZDB-PUB-181230-12
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.
Date: 2018
Source: The Journal of biological chemistry   294(8): 2732-2743 (Journal)
Registered Authors: Dong, Zhangji, Hu, Ping, Liang, Dong, Yao, Jihua, Yue, Yunyun, Zhao, Qingshun
Keywords: 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
PubMed: 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.