The Action of miR-148 in Human Target Gene

The Action of miR-148 in Human Target Gene
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The Action of miR-148 in Human Target Gene
What was the main hypothesis of the study?
The main hypothesis of the current study is that miR-148 represses the expression of the DNA methyltransferase (Dnmt3b) gene using a region in its coding sequence that is evolutionary conserved and available only in the Dnmt3b1, Dnmt3b2, and Dnmt3b4 splice variants but absent in Dnmt3b3.
What were the key previously-made observation(s) that led them to this hypothesis?
The hypothesis is based on the observation of miRNA repressing actions in plants where a very high-sequence complementarity is observed when the miRNA bind to the coding sequence of the proteins. Rhoades et al. (2002) showed that most miRNAs heavily interact with highly homologous proteins to regulate the expression of mRNAs. In line with this, Duursma et al. (2008) identified a site in Dnmt3b that could interact with 22 out of 23 nucleotides present in the miR-148a and miR-148b, making it close to the interaction observed in plants. The targeted site was also identified in mice, horses, armadillos, rhesus, and dogs providing its conservation in the evolutionary process. In addition, Lewis et al. (2005) conducted a study that identified site #2 in Dnmt3b that matched the miR-148 sequence without high levels of complementarity as the first site. Consequently, the researchers could hypothesize that miR-148 represses expression in the Dnmt3b gene.
What aspects of the interaction of miR-148 with its target sequence in the human Dnmt3b mRNA are unusual?
The unusual aspect of miR-148 interaction with the target sequence in the human Dnmt3b mRNA is that the effect of repression varies across the splice variants of the gene sequence. Overexpression of miR-148 was observed to contribute to the lowered expression of the Dnmt3b1 expression but had minimal results in the Dnmt3b splice due to its lack of the target site.
MicroRNAs can repress expression of target genes by either repressing translation of the mRNA and/or enhancing degradation of the mRNA target. Based on data presented in ...