A study released today shows that 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.
The research points toward a future treatment for post-stroke damage, which is often more extensive than the initial destruction that results when blood to the brain is temporarily shut off.
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?
The emerging evidence suggests that there may be more genes encoding regulatory RNAs than encoding proteins in the human genome, and that the amount and type of gene regulation in complex organisms has been substantially misunderstood for most of the past 50 years.
The application of genome tiling array technology and deep sequencing to the characterization of the transcriptome showed that there are tens of thousands of loci in mammals that express large transcripts that do not encode proteins, located intergenic, intronic and antisense to protein-coding genes.
The vast majority (at least 80%) of the human and mouse genomes are differentially transcribed in one context or another, with other studies reporting similar findings in all organisms examined. Indeed, it seems most intergenic (and by definition intronic) sequences are differentially transcribed, and therefore that the extent of the transcriptome expands with developmental complexity163.
"Less than 2 percent of the RNAs formed from the genome code for proteins, leaving 98 percent that we call 'noncoding RNA,'" says senior author Raghu Vemuganti, a professor of neurological surgery at the University of Wisconsin-Madison.
Moreover, those loci expressing lncRNAs show all of the hallmarks of bona fide genes4, including conservation of promoters indicative chromatin structure and regulation by conventional morphogens and transcription factors LncRNAs have been found to have a similar range of cellular half-lives as mRNAs and to be differentially expressed in a tissue-specific manner with higher resolution in the brain19
It has also become evident that many if not most protein-coding transcripts are targets for miRNA regulation that miRNAs can, in some cases, regulate large numbers of target mRNA , and reciprocally that many mRNAs contain target sites for many miRNAs although the implied regulatory logic of this complex multiplex arrangement has not been explained. The targets of miRNAs are usually thought to be mRNAs, but may also include other RNAs
In the study just published in the Journal of Neuroscience, Vemuganti and colleagues blocked one variety of long noncoding RNA (lncRNA), which exists in at least 40,000 unique varieties—possibly as many as 100,000.
"This lncRNA can bind to other RNA, to a protein, or to a protein on one side and DNA on the other," says first author Suresh Mehta "Among many other jobs, lncRNAs can regulate gene activity.
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