Blocking a type of RNA produced by what used to be called ‘junk DNA’ can prevent a significant portion of the neural destruction that follows a stroke, a new study in rats demonstrates.
The research also links two mysteries: Why does the majority of damage follow the restoration of blood supply? And what is the role of the vast majority of the human genome, which was once considered junk because it does not pattern for the RNA that makes proteins?
Note the expression: “once considered” junk.
“Stroke influences the expression of all types of RNA, and this RNA has a broad influence throughout the cell after the blood supply is restored, in what we call reperfusion injury” says Vemuganti. “A few years ago, our lab started to look at how stroke affects noncoding RNA. Two years ago, we identified about 200 types of various lncRNAs that greatly increase or decrease after stroke, and zeroed in on one that we named FosDT.
“We knew that the level of FosDT went up more than tenfold in the rat brain within three hours after the stroke,” adds Vemuganti. “We thought, if we block FosDT after the stroke, would it make any difference in the amount of structural damage or behavioral disability?”
Vemuganti and his colleagues designed three custom-made strands of RNA to silence FosDT, injected them into the rats, and deliberately shut off one artery in the brain for one hour. Tests performed within the first week showed that the treated rats regained motor skills much faster and more completely than control animals. Brain scans showed a significant reduction in the total volume of brain that was destroyed by the stroke.More.
FosDT stimulates a pathway to cell death, doubtless useful when called for but hardly a help after a stroke. Combating its influence may significantly limit post-stroke disability.
Note: The neo-Darwinian claim about “junk DNA” was that it does nothing (like the claimed vestigial organs), not that it was harmful. This study shows that FosDT does something harmful. That said, absent modern medicine, most life forms probably don’t survive a stroke, so from that perspective, this is uncharted territory.
See also: Junk DNA hires a PR firm
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Here’s the abstract:
Ischemia induces extensive temporal changes in cerebral transcriptome that influences the neurologic outcome after stroke. In addition to protein-coding RNAs, many classes of noncoding RNAs, including long noncoding RNAs (LncRNAs), also undergo changes in the poststroke brain. We currently evaluated the functional significance of an LncRNA called Fos downstream transcript (FosDT) that is cogenic with Fos gene. Following transient middle cerebral artery occlusion (MCAO) in adult rats, expression of FosDT and Fos was induced. FosDT knockdown significantly ameliorated the postischemic motor deficits and reduced the infarct volume. Focal ischemia also increased FosDT binding to chromatin-modifying proteins (CMPs) Sin3a and coREST (corepressors of the transcription factor REST). Furthermore, FosDT knockdown derepressed REST-downstream genes GRIA2, NF?B2, and GRIN1 in the postischemic brain. Thus, FosDT induction and its interactions with REST-associated CMPs, and the resulting regulation of REST-downstream genes might modulate ischemic brain damage. LncRNAs, such as FosDT, can be therapeutically targeted to minimize poststroke brain damage. (paywall) – S. L. Mehta, T. Kim, R. Vemuganti. Long Noncoding RNA FosDT Promotes Ischemic Brain Injury by Interacting with REST-Associated Chromatin-Modifying Proteins. Journal of Neuroscience, 2015; 35 (50): 16443 DOI: 10.1523/JNEUROSCI.2943-15.2015