What Regulates the Regulators

An article from Week in Science covers a topic of importance to genomic function- RNA editing. My comments follow in bold print. From the article:

The article mentions a mechanism called RNA editing amd some specific results associated with it. For example, ADAR, an enzyme, converts a nucleoside called adenosine, into inosine. This in turn can lead to altered expressions of genes among which are neurotransmitter genes.

Another form of editing involves microRNAs or miRNAs. These are non-coding RNAs known to have regulatory functions through their inactivation of mRNA. There is an editing process of precursor miRNA which can alter the activity of miRNA; amounting to the regulation of a regulatory element. As researcher Kazuko Nishikura notes:

“MicroRNAs often target a specific set of genes but when editing occurs, they may target a completely different set of genes. We used to believe there were only a limited number of RNA editing sites but now we think there may be as many as 20,000 sites involving perhaps 3,000 genes."

Regulatory mechanisms are themselves regulated by other mechanisms indicating an ordered system of layered genetic controls.

When examples of newly generated functions are cited how often do we witness regulatory functions on display, much less secondary layers of regulatory elements? Empirical evidence for them tends to be very indirect indeed.