We’re all asking ourselves these days, “But who regulates the regulators?” For miRNA, the answer may just be a consortium of genes both living and dead.
A group of Toronto researchers exogenously expressed versican 3’UTR (a potential target for miR-199a*) hooked up to a reporter construct. While expression of the luciferase or GFP reporter was diminished relative to controls, expression of the native versican protein itself was enhanced. Fibronectin, another extracellular matrix protein, is also a potential miR-199a* target. Lo and behold!, its expression also went up in cells and animals expressing the versican 3’UTR constructs. The assumption here is that the miR-199a* miRNA is being absorbed (co-opted, hijacked, …) by the exogenous target construct, allowing mRNA from the endogenous gene to at least partially escape regulation.
The researchers speculate that all the genomic detritus (like pseudogenes) that doesn’t seem to code for anything useful may, in fact, help to regulate the miRNA regulators. Perhaps the 20,000+ predicted pseudogenes in the human genome will make their way back into the spotlight. Follow their reasoning at PLoS One, February 2009