Abstract
MicroRNA (miRNA) are short non-coding RNA molecules that regulate multiple cellular processes, including development, cell differentiation, proliferation and death. Nevertheless, little is known on whether miRNA control the same gene networks in different tissues. miR-709 is an abundant miRNA expressed ubiquitously. Through transcriptome analysis, we have identified targets of miR-709 in hepatocytes. miR-709 represses genes implicated in cytoskeleton organization, extracellular matrix attachment, and fatty acid metabolism. Remarkably, none of the previously identified targets in non-hepatic tissues are silenced by miR-709 in hepatocytes, even though several of these genes are abundantly expressed in liver. In addition, miR-709 is upregulated in hepatocellular carcinoma, suggesting it participates in the genetic reprogramming that takes place during cell division, when cytoskeleton remodeling requires substantial changes in gene expression. In summary, the present study shows that miR-709 does not repress the same pool of genes in separate cell types. These results underscore the need for validating gene targets in every tissue a miRNA is expressed.
Highlights
MicroRNAs are a class of small (~19–23 nt) non-coding RNAs that are widely expressed in plants, animals, and some viruses
MiR-709 is an abundant miRNA expressed in multiple mouse tissues, including brain, thymus, heart, lung, liver, spleen, kidney, adipose tissue, and testes14–17. miR-709 is embedded in intron 8 of the Regulatory Factor X1 (Rfx1) gene, a member of the winged-helix subfamily of helix-turn-helix transcription factors with activation as well as repression activity[18]
The degree of luciferase repression was ~3-fold below the level observed with a tough decoy containing a target site for miR-122, the most abundant miRNA in liver, which is consistent with the amount of miR-709 relative to miR-122 (Supplementary Table 1)
Summary
MicroRNAs (miRNAs) are a class of small (~19–23 nt) non-coding RNAs that are widely expressed in plants, animals, and some viruses. It is widely accepted that miRNAs have important roles in regulating complex processes such as development[6], cell cycle[7], and metabolism[8] Their role as regulators of gene expression is paradoxical. MiRNAs expressed in multiple tissues would be predicted to bind to and regulate the same genes in these tissues, as long as the mRNAs were part of the tissue’s transcriptome. It is not known whether miR-709, a ubiquitous miRNA, regulates the same genes in different tissues. We have used a comprehensive approach to identify liver targets of miR-709, with special emphasis on analysis of previously validated targets in non-hepatic tissues
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