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It slices, it dices, it silences: ADAR1 as gene-silencing modular RNA multitool
Date:5/1/2013

RNA, once considered a bit player in the grand scheme by which genes encode protein, is increasingly seen to have a major role in human genetics. In a study presented in the April 25 issue of the journal Cell, researchers from The Wistar Institute discovered how the RNA-editing protein, ADAR1, also combines with the protein called Dicer to create microRNA (miRNA) and small interfering (siRNA). These varieties of RNA, in turn, play a crucial role in gene regulation--silencing or "switching off" the production of specific proteins.

Upward of 60 percent of mammalian genes are thought to be targeted and regulated by non-coding RNA molecules, researchers say. This aspect of RNA biology is so critical to life, in fact, that the Nishikura laboratory demonstrated how a lack of ADAR1 was lethal in embryonic mice.

"Our evidence suggests that regulation of the microRNA synthesis is critical for life, and we have determined that the regulation is orchestrated by the RNA editing protein ADAR1," said Kazuko Nishikura, Ph.D., a professor in Wistar's Gene Expression and Regulation program and senior author of the study. "We see here this remarkable evolutionary ingenuity, where ADAR1 can combine with other enzymes to serve different roles in RNA functions, like a molecular Swiss army knife."

The genome, in the form of DNA, contains the instructions for both new proteins and the RNA that helps regulate how protein production is controlled. No longer just seen in the form messenger RNA (mRNA)--delivering transcribed genetic blueprints from DNA to the cellular factories that build proteins. Numerous varieties of RNA, such as non-coding RNA, have been described that hold important roles in many facets of our cellular biology. "Non-coding RNA that do not code for proteins seem to have an overt and pervasive role in overseeing our genome," Nishikura said.

For more than 20 years following the discovery and definition of the ADAR family o
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Contact: Greg Lester
glester@wistar.org
215-898-3934
The Wistar Institute
Source:Eurekalert

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