Researchers Explore Genetic Molecular Mechanisms Behind Stroke and Autism

DNA may be the building block of all organic matter but it actually has no power or function on its own.  In order for DNA to enforce its genetic mechanisms—and transform gene into proteins—it must first be transcribed into RNA. This is a delicate molecule in the brain which, effectively tunes genes into whatever protein the body needs, when the body requires it.

Robert and Harriet Heilbrunn Professor Robert B. Darnell describes, “Gene expression is a lot more complicated than turning on a switch. There’s a whole layer of regulation that alters both the quality and quantity of a protein that’s produced from a gene. And much of it happens at the level of RNA.”

But when this process—of transforming DNA to RNA—goes awry, it can yield very serious consequences.  Professor Darnell’s study, however, has quite recently found the brain responds to stroke with an extremely specific regulation of a particular RNA subtype. In addition, Darnell’s research team also learned certain genetic mutations can influence gene regulation, which also, apparently, is a baseline for autism spectrum disorder. 

Effectively, when DNA is held safe within a cell, RNA has a lot of mobility.  When in the brain, however, messenger RNA likes to hang out at neural connections—the synapses, where they can be translated into proteins that affect brain signaling.  This process is actually regulated by an entirely different class of RNA (microRNA) which has the ability to quickly promote or suppress the production of proteins as a natural response to other big changes in the brain. 

Experimenting with RNA, then, Darnell’s team tracked microRNA activity in the brain of a mouse after a simulated stroke. Through the use of a novel technique called crosslinking immunoprecipitation (CLIP), they found that stroke events seem to prompt a massive reduction in one subset of microRNA, called miR-29.  These molecules, apparently, inhibit the production of two proteins—GLT-1 and aquaporin—and when this is combined with a drop in miR-29 levels, the brain overcompensates by overproducing these two other molecules. 

The job of GLT-1 is to get rid of extra glutamate, which is produced en masse during a stroke event; and can damage the brain if not restored to normal.  Any uptick in production of this protein appears to stem stroke-associated brain damage.  Higher aquaporin levels, though, appears to worsen tissue swelling, which can exacerbate any existing brain damage (as in a stroke event).  


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