December 25, 2011 | 2
It’s a long way from gene to protein. The dogmatic scenario is: DNA gets transcribed into RNA, which gets translated into protein. But in real life, and in real living things, the workings aren’t quite that simple.
One example: individual units of RNA sometimes need to be converted, in what’s called RNA editing, into related entities for the ultimate formation of the right proteins. An enzyme called ADAR (adenosine deaminase, RNA-specific) is responsible for a specific such alteration important for good nervous system function.
Now researchers have devised a technique for seeing this particular RNA editing process in real time—the corrected strand gives off a green glow—and even for the restoration of functionality. “We can take a mutant version of a gene and restore its function,” Brown University’s Robert Reenan explained in a prepared statement. The findings were described online Sunday in the journal Nature Methods (Scientific American is part of Nature Publishing Group).
Reenan and colleagues produced fruit flies that included an altered version of the gene for the oft-used lab tool green fluorescent protein. The protein product of their genetic construct would not glow—until it was first repaired by ADAR. “We’re actually repairing RNA at the level of a single informational bit, or nucleotide,” Reenan said.
By following the green glow, the team was able to track the patterns of ADAR in the fruit flies’ brains in vivo. “We designed the molecular reporter to give us a fluorescent readout from living organisms,” Reenan said.
Because the technique actually repairs an error and restores a function, it suggests promise for gene therapy-based treatments—but at the RNA rather than DNA level. Such treatment would target transcription mistakes, which may contribute to diseases such as epilepsy, schizophrenia and suicidal depression.
Reenan and colleagues have previously described connections between ADAR function and a fruit fly model for Fragile X mental retardation, caused by a mutation on the X chromosome. If the new tool can expose correlations between ADAR activity and disease states, it could reveal the role of RNA editing errors in the genesis of those syndromes.
Future research will reveal whether the green glow technique gets a green light to help researchers study—and maybe even treat—gene-related neurological diseases in humans.
Steve Mirsky contributed to this story.