Evolution of themiR199-214cluster and vertebrate skeletal development

Abstract

The miR199 and miR214 genes occupy an intronic cluster located on the opposite strand of the Dynamin3 gene. These miRNAs play major roles in a broad variety of developmental processes and diseases, including skeletal development and several types of cancer. In the work reported here, we first deciphered the origin of the miR199 and miR214 families by following evolution of miR paralogs and their host Dynamin paralogs. We then examined the expression patterns of miR199 and miR214 in developing zebrafish embryos and demonstrated their regulation through a common primary transcript. Results suggest an evolutionarily conserved regulation across vertebrate lineages. Our expression study showed predominant expression patterns for both miR in tissues surrounding developing craniofacial skeletal elements consistent with expression data in mouse and human, thus indicating a conserved role of miR199 and miR214 in vertebrate skeletogenesis.

Peroxisome Proliferator-activated Receptor-α-mediated Transcription of miR-199a2 Attenuates Endothelin-1 Expression via Hypoxia-inducible Factor-1α

“…miR-199a2 is located within the DNM3os transcription unit. This long noncoding RNA transcript is responsible for synthesis of the miRNA cluster containing miR-199a2 and miR-214 and is involved in skeletal development (42,43). Accordingly it was necessary to determine whether PlGF regulated synthesis of the long DNM3os transcript, as previously observed, or instead led to independent transcription of premir-199a2.…”

miR-214 promotes osteoclastogenesis by targeting Pten/PI3k/Akt pathway

“…37 The expression study showed predominant expression patterns for miR-199-214 cluster in tissues surrounding developing craniofacial skeletal elements and indicated a conserved role of miR-199 and miR-214 in vertebrate skeletogenesis. 38 miR-199-214 is essential to skeletogenesis because miR-199-214 cluster knockout mice display skeletal abnormalities. 20 In our study, we found that miR-214 plays an important role in osteoclastogenesis and affects osteoclast activity through regulating the expression of osteoclast functional genes.…”

Expanding the annotation of zebrafish microRNAs based on small RNA sequencing

“…The zebrafish smallRNA-seq dataset clearly contained three pairs of mirror-mirs (Table 1), which are defined as a pair of mir genes originating from overlapping genomic regions but on opposite strands (Tyler et al, 2008; Scott et al, 2012). For example, the expression of mir3120 , mirror-mir of mir214 , has been described in mammals but in no other species (Scott et al, 2012; Desvignes et al, 2014). Here we show that miR3120 , a mature fragment originating from the mirror-mir of mir214 , is expressed in adult zebrafish.…”