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Penn researchers discover how microRNAs control protein synthesis

PHILADELPHIA While most RNAs work to create, package, and transfer proteins as determined by the cells immediate needs, miniature pieces of RNA, called microRNAs (miRNAs) regulate gene expression. Recently, researchers from the University of Pennsylvania School of Medicine determined how miRNAs team up with a regulatory protein to halt protein production. Results of the study were published recently in Cell.

Scientists estimate miRNAs have the ability to regulate the expression of approximately one third of human genes, and previous studies have linked abnormal activity of miRNAs to cancer and other diseases.

While scientists know that most miRNAs in mammals repress the translation of RNA to protein, the molecular steps by which they achieve regulation are largely unknown. By studying the relationship between human miRNAs and the regulatory protein Argonaute2 (Ago2), lead author Marianthi Kiriakidou, MD, Assistant Professor of Medicine, and others set out to uncover how miRNAs control protein synthesis.

Before interfering with protein production, miRNAs associate with proteins from the Argonaute (Ago) family. According to Kiriakidou, Ago proteins are at the heart of the miRNA regulatory pathway, due to their engagement with miRNAs.

The miRNA and Ago protein association dictates the way that miRNA regulates gene production. While there are four different proteins in the human Ago family, Kiriakidou and colleagues from Zissimos Mourelatos team focused on the interaction between miRNA and Ago2. Ago2 stands out among the four mammalian Ago proteins since it is the only Ago protein able to mediate RNA interference by inhibiting gene expression.

Under normal conditions, the initiation of protein synthesis is kicked off when a protein called eIF4E binds to the front end, or cap, of messenger RNA. With eIF4E in place, a cascade of protein-protein and protein-RNA interactions allows the manufacturing of proteins to begi
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Contact: Karen Kreeger
karen.kreeger@uphs.upenn.edu
215-349-5658
University of Pennsylvania School of Medicine
9-Jul-2007


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