Evidence for the conservation of miR-223 in zebrafish (Danio rerio): Implications for function

• Published in: Gene 2015-07, Vol.566 (1), p.54-62
• Main Authors: Roberto, V.P., Tiago, D.M., Gautvik, K., Cancela, M.L.
• Format: Article
• Language: English
• Subjects: Animals; Cloning, Molecular; Conservation; Danio rerio; Evolution, Molecular; Freshwater; Haematopoiesis; Hematopoiesis; Humans; Mammals - genetics; Mammals - metabolism; MicroRNAs - genetics; MicroRNAs - metabolism; miR-223; miRNA expression; miRNA targets; Osteoclastogenesis; Osteoclasts - cytology; Phylogeny; Zebrafish - genetics; Zebrafish - metabolism
• ISSN: 0378-1119; 1879-0038
• DOI: 10.1016/j.gene.2015.04.022

MicroRNAs (miRNAs) are an abundant and conserved class of small RNAs, which play important regulatory functions by interacting with the 3′ untranslated region (UTR) of target mRNAs. Through this mechanism, miR-223 was shown to regulate genes involved in mammalian haematopoiesis, both in physiological and pathological contexts. MiR-223 is essential for normal myelopoiesis in mammals, promoting granulocyte, osteoclast and megakaryocyte differentiation and suppressing erythropoiesis. However, there is a general lack of knowledge regarding miR-223 function in other vertebrates, which could help to clarify its role in other processes, such as development. In this work, we explored the functional conservation of miR-223 using zebrafish as a model. We show that miR-223 gene structure and genomic context have been maintained between human and zebrafish. In addition, we identified 22 novel sequences of miR-223 precursor and demonstrate that it contains domains highly conserved among vertebrates, suggesting function preservation throughout evolution. Furthermore, collected evidences show that miR-223 expression is highly correlated with haematopoietic events and osteoclastogenesis throughout zebrafish development. In adults, expression of miR-223 in zebrafish tissues mimics the distribution in mice, with high levels found in the major fish haematopoietic organ, the head kidney. These results suggest a conservation of miR-223 role in haematopoiesis, and osteoclastogenesis between zebrafish and human. Accordingly, validated targets of miR-223 in mammalian models were investigated and defined as putative targets in zebrafish, by in silico and gene expression analysis. Our data compiles critical evidence showing that miR-223, a highly conserved miRNA, appears to have kept similar regulatory functions throughout evolution. •miR-223 gene structure and genomic contexts are maintained between zebrafish and human.•Primary and secondary structures of miR-223 precursors are conserved across 42 vertebrate species.•miR-223 expression throughout zebrafish development correlates with haematopoietic and osteoclastogenic events.•miR-223 is highly expressed in the major haematopoietic organs of zebrafish and mouse.•Validated mammalian targets of miR-223 are putative targets in zebrafish.