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


ABSTRACT: 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.

SUBMITTER: Jia W 

PROVIDER: S-EPMC6393615 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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

Jia Wenshuang W   Liang Dong D   Li Nan N   Liu Meijing M   Dong Zhangji Z   Li Jingyun J   Dong Xiaohua X   Yue Yunyun Y   Hu Ping P   Yao Jihua J   Zhao Qingshun Q  

The Journal of biological chemistry 20181228 8


Zebrafish <i>gata4/5/6</i> 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 <i>gata4/5/6-</i>regulated processes. Performing RNA-Seq deep sequencing analysis of the expression changes of microRNAs in <i>gata4/5/6-</i>knockdown embryos, we identified miR-210-5p as a regulator of zebrafish primitive myelopoiesis. Knocking down <i>gata4/5/6</i> (generating <i>gata5/6</i> morphants)  ...[more]

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