PMID- 11861913 OWN - NLM STAT- MEDLINE DCOM- 20020311 LR - 20190501 IS - 1362-4962 (Electronic) IS - 0305-1048 (Print) IS - 0305-1048 (Linking) VI - 30 IP - 5 DP - 2002 Mar 1 TI - The 3'-untranslated regions of cytoskeletal muscle mRNAs inhibit translation by activating the double-stranded RNA-dependent protein kinase PKR. PG - 1205-12 AB - 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. FAU - Nussbaum, Jean M AU - Nussbaum JM AD - Department of Biochemistry and Molecular Biology, New Jersey Medical School, UMDNJ, 185 South Orange Avenue, Newark, NJ 07103-2714, USA. FAU - Gunnery, Shobha AU - Gunnery S FAU - Mathews, Michael B AU - Mathews MB LA - eng GR - R01 AI034552/AI/NIAID NIH HHS/United States GR - AI34552/AI/NIAID NIH HHS/United States PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - England TA - Nucleic Acids Res JT - Nucleic acids research JID - 0411011 RN - 0 (3' Untranslated Regions) RN - 0 (Actins) RN - 0 (Cytoskeletal Proteins) RN - 0 (Muscle Proteins) RN - 0 (Tropomyosin) RN - 0 (Troponin) RN - EC 2.7.11.1 (eIF-2 Kinase) SB - IM MH - 3' Untranslated Regions/metabolism/*pharmacology MH - Actins/genetics MH - Animals MH - Cytoskeletal Proteins/*genetics MH - Electrophoretic Mobility Shift Assay MH - Enzyme Activation MH - Muscle Proteins/*genetics MH - Nucleic Acid Conformation MH - *Protein Biosynthesis MH - Rabbits MH - Reticulocytes/metabolism MH - Tropomyosin/genetics MH - Troponin/genetics MH - eIF-2 Kinase/*metabolism PMC - PMC101232 EDAT- 2002/02/28 10:00 MHDA- 2002/03/12 10:01 PMCR- 2002/03/01 CRDT- 2002/02/28 10:00 PHST- 2002/02/28 10:00 [pubmed] PHST- 2002/03/12 10:01 [medline] PHST- 2002/02/28 10:00 [entrez] PHST- 2002/03/01 00:00 [pmc-release] AID - gkf192 [pii] AID - 10.1093/nar/30.5.1205 [doi] PST - ppublish SO - Nucleic Acids Res. 2002 Mar 1;30(5):1205-12. doi: 10.1093/nar/30.5.1205.