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Nucleic Acids Research, 2002, Vol. 30, No. 5 1205-1212
© 2002 Oxford University Press

The 3'-untranslated regions of cytoskeletal muscle mRNAs inhibit translation by activating the double-stranded RNA-dependent protein kinase PKR

Jean M. Nussbaum, Shobha Gunnery and Michael B. Mathews*

Department of Biochemistry and Molecular Biology, New Jersey Medical School, UMDNJ, 185 South Orange Avenue, Newark, NJ 07103-2714, USA

Cytoskeletal proteins are associated with actin in the microfilaments and have a major role in microfilament assembly and function. The expression of some of these proteins has been implicated in cell growth and transformation. Specifically, the 3'-untranslated regions (3'-UTRs) of tropomyosin, troponin and cardiac actin can induce muscle cell differentiation and appear to function as tumor suppressors. These RNA sequences are predicted to fold to form secondary structures with extended stretches of duplex. We show that the 3'-UTRs of the cytoskeletal mRNAs interact with the RNA-binding domain of the RNA-activated protein kinase PKR. Correspondingly, these RNAs activate PKR in vitro and inhibit globin translation in the rabbit reticulocyte lysate translation system. These data are consistent with a mechanism whereby PKR mediates the differentiation- and tumor-related actions of the cytoskeletal 3'-UTR sequences.

* To whom correspondence should be addressed. Tel: +1 973 972 4411; Fax: +1 973 972 5594; Email: mathews{at}umdnj.edu Present address:Jean M. Nussbaum, Department of Chemistry, University of Saint Francis, 2701 Spring Street, Fort Wayne, IN 46808, USA


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