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'Activating' RNA takes DNA on a loop through time and space
Date:2/17/2013

oding RNAs are probably one of the earliest molecules that determine spatial and temporal gene expression in a developing embryo," Shiekhattar said. "These enhancers can help turn genes on and off as a growing embryo would need, but as we have seen in other genetic mechanisms of embryonic development, they can lead to cancer if they are switched on inappropriately in adult cells."

In the classic "central dogma" of biology, chromosomal DNA is transcribed into RNA, which is then translated by the cell into proteins. In recent years, however, scientists have found that not all transcribed RNA molecules become translated into proteins. In fact, studies have shown that large portions of the genome are transcribed into RNA that serve tasks other than functioning as blueprints for proteins. In 2010, the Shiekhattar lab first published the discovery of these ncRNA enhancer molecules in the journal Cell (2010 Oct 1;143(1):46-58), and theorized on their role as "enhancers" of gene expression. Since then, laboratories around the world have published and linked ncRNAs not only to transcriptional enhancers but also to certain diseases, including some cancers.

To discover how such enhancer-like RNAs function, the Shiekhatter laboratory deleted candidate molecules with known roles in activating gene expression, and assessed if they were related to RNA-dependent activation. They found that depleting components of the protein complex known as Mediator specifically and potently diminished the ability of ncRNA-a to start the process of transcribing a gene into RNA. Further, they found that these activating ncRNAs can attach to Mediator at multiple locations within the Mediator protein complex, and Mediator itself can interact with the enhancer element site on DNA that encodes these activating ncRNAs. Their results also determined how mutations in a protein that makes up the Mediator complex, called MED12, drastically diminishes Mediator's ability to associate with ac
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Contact: Greg Lester
glester@wistar.org
215-898-3934
The Wistar Institute
Source:Eurekalert

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