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:: Posted by American Biotechnologist on 10-10-2013
Harvard Stem Cell Institute (HSCI) researchers have settled a century-old debate over whether occurrence of DNA methylation acts to silence gene expression, or if genes are turned off by other means before they are methylated.
As explicated today in the journal Nature, methylation in fact enforces gene silencing, and it is levels of a newly identified form of RNA produced by individual genes that determines whether they are turned off by the addition of a methyl (CH3) group by the enzyme DNA methylase 1 (DNMT1).
The study, led by HSCI Principal Faculty member Daniel Tenen, MD, found that during transcription of DNA to RNA, a gene produces a small amount of what the investigators named “extracoding RNA,” which stays in the nucleus and binds to DNMT1, blocking its ability to methylate, or silence the gene. The discovery of RNA’s new function has therapeutic potential as an on-off switch for gene expression.
:: Posted by American Biotechnologist on 08-21-2013
Often, it is easy to get caught up studying the “movers and shakers” of our favorite biological system while tragically ignoring the role of a smaller player and wrongfully endowing it with the title of an “unimportant” molecule. Yet until every biological nook and cranny are uncovered, nothing should ever be dismissed as irrelevant.
Researchers at the University of Pennsylvania had a chance to demonstrate this principle recently as they revealed that a scarce, small RNA, called U6atac, controls the expression of hundreds of genes that have critical functions in cell growth, cell-cycle control, and global control of physiology.
While the major spliceosomes that control the process of removing the majority of introns from mRNA prior to their translation into protein have been studied for years, few scientists have ventured into the world of the minor spliceosome as it was thought to only control the post-transcriptional processing of very few mRNA molecules. Bucking the trend, Dr. Gideon Dreyfuss and his team from U Penn concentrated their efforts on studying the role of the minor spliceosomes and their results have revealed an heretofore undiscovered mechanism responsible for controlling the expression of hundreds of human genes.
Long segments of RNA—encoded in our DNA but not translated into protein—are key to physically manipulating DNA in order to activate certain genes. These non-coding RNA-activators (ncRNA-a) have a crucial role in turning genes on and off during early embryonic development, researchers say, and have also been connected with diseases, including some cancers, in adults.
In an online article of the journal Nature, a team of scientists led by Wistar’s Ramin Shiekhattar, Ph.D., detail the mechanism by which long non-coding RNA-activators promote gene expression. They show how these RNA molecules help proteins in the cell to create a loop of DNA in order to open up genes for transcription. Their experiments have also described how particular ncRNA-a molecules are related to FG syndrome, a genetic disease linked to severe neurological and physical deficits.