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Changing genetic 'red light' to green holds promise for treating disease
Date:6/15/2011

he way through and create a normal, full-length protein. The team produced these results both in vitro and in live yeast cells.

"This is a very exciting finding," said Yi-Tao Yu, Ph.D., lead study author and associate professor of Biochemistry and Biophysics at the Medical Center. "No one ever imagined that you could alter a stop codon the way we have and allow translation to continue uninterrupted like it was never there in the first place."

The findings are important because current estimates suggest that approximately one third of genetic diseases are caused by the presence of pre-mature stop codons that result in shortened proteins. The results could aid the development of treatment strategies designed to help the body override stop codons and produce adequate amounts of full-length proteins, whose absence causes diseases like cystic fibrosis and contributes to different types of cancer.

Yu, along with first author John Karijolich, Ph.D., used another type of RNA guide RNA to modify messenger RNA. Guide RNAs are short RNAs that bind to specific sequences in RNA and allow just one particular site to be modified. "Guide RNAs give us tremendous power to zero in on one spot in the genome and make very targeted changes," noted Bambara.

The team developed an artificial guide RNA and programmed it to target and change a specific stop codon in an mRNA.

"The fact that this strategy worked that the guide RNA we created found its way to its target, the stop codon, and directed the desired structure change is pretty remarkable. Guide RNAs weren't thought to have access to messenger RNA, so no one believed they could target messenger RNA for modification," said Karijolich, who conducted the research as a graduate student at Rochester, but is now a postdoctoral fellow in the Department of Biochemistry at the Robert Wood Johnson Medical School. "Our results bring up the question of whether a similar process may be happening
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Contact: Emily Boynton
emily_boynton@urmc.rochester.edu
585-273-1757
University of Rochester Medical Center
Source:Eurekalert

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