Sequences responsible for intracellular localization of beta-actin messenger RNA also affect cell phenotype

doi:10.1083/jcb.127.2.441

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Sequences responsible for intracellular localization of beta-actin messenger RNA also affect cell phenotype

EH Kislauskis, X Zhu and RH Singer
Department of Cell Biology, University of Massachusetts Medical Center, Worcester 01655.

We have characterized the structure and function of RNA sequences that direct beta-cytoplasmic actin mRNA to the cell periphery were mapped to two segments of 3'-untranslated region by expression of LacZ/beta-actin chimeric mRNAs in chicken embryo fibroblasts (CEFs). A 54-nt segment, the "RNA zipcode," and a homologous but less active 43-nt segment each localized beta-galactosidase activity to the leading lamellae. This zipcode contains the full activity, and mutations or deletions within it reduce, but do not eliminate, its activity, indicating that several motifs contribute to the activity. Two of these motifs, when multimerized, can regenerate almost full activity. These sequences are highly conserved in evolution, since the human beta-actin zipcode, positioned identically in the 3'UTR localizes equally well in chicken cells. Complementary phosphorothioate oligonucleotides against the zipcode delocalized endogenous beta-actin mRNA, whereas those complementary to the region just outside the zipcode, or sense oligonucleotides, did not. Actin mRNA or protein levels were unaffected by the antisense treatments, but a dramatic change in lamellipodia structure, and actin stress fiber organization was observed using the same antizipcode oligonucleotides which delocalized the mRNA. Hence, discrete 3'UTR sequences direct beta-actin isoform synthesis to the leading lamellae and affect cell morphology, presumably through the actin cytoskeleton.
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Roper, K., Mao, Y., Brown, N. H. (2005). Contribution of sequence variation in Drosophila actins to their incorporation into actin-based structures in vivo. J. Cell Sci. 118: 3937-3948 [Abstract] [Full Text]
Dugre-Brisson, S., Elvira, G., Boulay, K., Chatel-Chaix, L., Mouland, A. J., DesGroseillers, L. (2005). Interaction of Staufen1 with the 5' end of mRNA facilitates translation of these RNAs. Nucleic Acids Res 33: 4797-4812 [Abstract] [Full Text]
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Abdollahi, M R, Gaunt, T R, Syddall, H E, Cooper, C, Phillips, D I W, Ye, S, Day, I N M (2005). Angiotensin II type I receptor gene polymorphism: anthropometric and metabolic syndrome traits. J. Med. Genet. 42: 396-401 [Abstract] [Full Text]
REDDY, K. K., OITOMEN, F. M., PATEL, G. P., BAG, J. (2005). Perinuclear localization of slow troponin C m RNA in muscle cells is controlled by a cis-element located at its 3' untranslated region. RNA 11: 294-307 [Abstract] [Full Text]
Yan, J., Marr, T. G. (2005). Computational analysis of 3'-ends of ESTs shows four classes of alternative polyadenylation in human, mouse, and rat. Genome Res 15: 369-375 [Abstract] [Full Text]
Wang, H., Tiedge, H. (2004). Translational Control at the Synapse. Neuroscientist 10: 456-466 [Abstract]
Coventry, A., Kleitman, D. J., Berger, B. (2004). MSARI: Multiple sequence alignments for statistical detection of RNA secondary structure. Proc. Natl. Acad. Sci. USA 101: 12102-12107 [Abstract] [Full Text]
Kress, T. L., Yoon, Y. J., Mowry, K. L. (2004). Nuclear RNP complex assembly initiates cytoplasmic RNA localization. JCB 165: 203-211 [Abstract] [Full Text]
Yaniv, K., Fainsod, A., Kalcheim, C., Yisraeli, J. K. (2003). The RNA-binding protein Vg1 RBP is required for cell migration during early neural development. Development 130: 5649-5661 [Abstract] [Full Text]
Rossoll, W., Jablonka, S., Andreassi, C., Kroning, A.-K., Karle, K., Monani, U. R., Sendtner, M. (2003). Smn, the spinal muscular atrophy-determining gene product, modulates axon growth and localization of {beta}-actin mRNA in growth cones of motoneurons. JCB 163: 801-812 [Abstract] [Full Text]
Lee, S.-K., Hollenbeck, P. J. (2003). Organization and translation of mRNA in sympathetic axons. J. Cell Sci. 116: 4467-4478 [Abstract] [Full Text]
Goetze, B., Grunewald, B., Kiebler, M. A., Macchi, P. (2003). Coupling the Iron-Responsive Element to GFP--An Inducible System to Study Translation in a Single Living Cell. Sci Signal 2003: pl12-pl12 [Abstract] [Full Text]
LERNER, R. S., SEISER, R. M., ZHENG, T., LAGER, P. J., REEDY, M. C., KEENE, J. D., NICCHITTA, C. V. (2003). Partitioning and translation of mRNAs encoding soluble proteins on membrane-bound ribosomes. RNA 9: 1123-1137 [Abstract] [Full Text]
Sacks, L. D., Cann, G. M., Nikovits, W. Jr, Conlon, S., Espinoza, N. R., Stockdale, F. E. (2003). Regulation of myosin expression during myotome formation. Development 130: 3391-3402 [Abstract] [Full Text]
Houle, V. M., Li, W., Montgomery, R. K., Grand, R. J. (2003). mRNA localization in polarized intestinal epithelial cells. Am. J. Physiol. Gastrointest. Liver Physiol. 284: G722-G727 [Abstract] [Full Text]
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Itoh, M., Haga, I., Li, Q.-H., Fujisawa, J.-i. (2002). Identification of cellular mRNA targets for RNA-binding protein Sam68. Nucleic Acids Res 30: 5452-5464 [Abstract] [Full Text]
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Iseli, C., Stevenson, B. J., de Souza, S. J., Samaia, H. B., Camargo, A. A., Buetow, K. H., Strausberg, R. L., Simpson, A. J.G., Bucher, P., Jongeneel, C. V. (2002). Long-Range Heterogeneity at the 3' Ends of Human mRNAs. Genome Res 12: 1068-1074 [Abstract] [Full Text]
Snee, M., Kidd, G. J., Munro, T. P., Smith, R. (2002). RNA trafficking and stabilization elements associate with multiple brain proteins. J. Cell Sci. 115: 4661-4669 [Abstract] [Full Text]
Zheng, J.-Q., Kelly, T. K., Chang, B., Ryazantsev, S., Rajasekaran, A. K., Martin, K. C., Twiss, J. L. (2001). A Functional Role for Intra-Axonal Protein Synthesis during Axonal Regeneration from Adult Sensory Neurons. J. Neurosci. 21: 9291-9303 [Abstract] [Full Text]
Aronov, S., Aranda, G., Behar, L., Ginzburg, I. (2001). Axonal Tau mRNA Localization Coincides with Tau Protein in Living Neuronal Cells and Depends on Axonal Targeting Signal. J. Neurosci. 21: 6577-6587 [Abstract] [Full Text]
Shestakova, E. A., Singer, R. H., Condeelis, J. (2001). The physiological significance of beta -actin mRNA localization in determining cell polarity and directional motility. Proc. Natl. Acad. Sci. USA 98: 7045-7050 [Abstract] [Full Text]
Gunning, P., Ferguson, V, Brennan, K., Hardeman, E. (2001). Alpha-skeletal actin induces a subset of muscle genes independently of muscle differentiation and withdrawal from the cell cycle. J. Cell Sci. 114: 513-524 [Abstract]
Song, J., Worth, N. F., Rolfe, B. E., Campbell, G. R., Campbell, J. H. (2000). Heterogeneous Distribution of Isoactins in Cultured Vascular Smooth Muscle Cells Does Not Reflect Segregation of Contractile and Cytoskeletal Domains. J. Histochem. Cytochem. 48: 1441-1452 [Abstract] [Full Text]
Coulis, C. M., Lee, C., Nardone, V., Prokipcak, R. D. (2000). Inhibition of c-myc Expression in Cells by Targeting an RNA-Protein Interaction Using Antisense Oligonucleotides. Mol. Pharmacol. 57: 485-494 [Abstract] [Full Text]
Morris, E., Evason, K, Wiand, C, L'Ecuyer, T., Fulton, A. (2000). Misdirected vimentin messenger RNA alters cell morphology and motility. J. Cell Sci. 113: 2433-2443 [Abstract]
Dvorak, A. M., Morgan, E. S., Lichtenstein, L. M., Weller, P. F., Schleimer, R. P. (2000). RNA Is Closely Associated with Human Mast Cell Secretory Granules, Suggesting a Role(s) for Granules in Synthetic Processes. J. Histochem. Cytochem. 48: 1-12 [Abstract] [Full Text]
Li, W., Wang, J., Coluccio, L. M., Matsudaira, P., Grand, R. J. (2000). Brush Border Myosin I (BBMI): A Basally Localized Transcript in Human Jejunal Enterocytes. J. Histochem. Cytochem. 48: 89-94 [Abstract] [Full Text]
Meagher, R. B., McKinney, E. C., Kandasamy, M. K. (1999). Isovariant Dynamics Expand and Buffer the Responses of Complex Systems: The Diverse Plant Actin Gene Family. Plant Cell 11: 995-1006 [Full Text]
BASSELL, G. J., OLEYNIKOV, Y., SINGER, R. H. (1999). The travels of mRNAs through all cells large and small. FASEB J. 13: 447-454 [Full Text]
Shestakova, E. A., Wyckoff, J., Jones, J., Singer, R. H., Condeelis, J. (1999). Correlation of {beta}-Actin Messenger RNA Localization with Metastatic Potential in Rat Adenocarcinoma Cell Lines. Cancer Res. 59: 1202-1205 [Abstract] [Full Text]
Scaturro, M., Nastasi, T., Raimondi, L., Bellafiore, M., Cestelli, A., Di Liegro, I. (1998). H10 RNA-binding Proteins Specifically Expressed in the Rat Brain. J. Biol. Chem. 273: 22788-22791 [Abstract] [Full Text]
Macdonald, P. M., Kerr, K. (1998). Mutational Analysis of an RNA Recognition Element That Mediates Localization of bicoid mRNA. Mol. Cell. Biol. 18: 3788-3795 [Abstract] [Full Text]
Havin, L., Git, A., Elisha, Z., Oberman, F., Yaniv, K., Schwartz, S. P., Standart, N., Yisraeli, J. K. (1998). RNA-binding protein conserved in both microtubule- and microfilament-based RNA�localization. Genes Dev. 12: 1593-1598 [Abstract] [Full Text]
Fages, C, Kaksonen, M, Kinnunen, T, Punnonen, E., Rauvala, H (1998). Regulation of mRNA localization by transmembrane signalling: local interaction of HB-GAM (heparin-binding growth-associated molecule) with the cell surface localizes beta-actin mRNA. J. Cell Sci. 111: 3073-3080 [Abstract]
Watanabe, H, Kislauskis, E., Mackay, C., Mason-Savas, A, Marks, S. (1998). Actin mRNA isoforms are differentially sorted in normal osteoblasts and sorting is altered in osteoblasts from a skeletal mutation in the rat. J. Cell Sci. 111: 1287-1292 [Abstract]
Wallace, C. S., Lyford, G. L., Worley, P. F., Steward, O. (1998). Differential Intracellular Sorting of Immediate Early Gene mRNAs Depends on Signals in the mRNA Sequence. J. Neurosci. 18: 26-35 [Abstract] [Full Text]
Vaduva, G., Martin, N. C., Hopper, A. K. (1997). Actin-binding Verprolin Is a Polarity Development Protein Required for the Morphogenesis and Function of the Yeast Actin Cytoskeleton. JCB 139: 1821-1833 [Abstract] [Full Text]
Knowles, R. B., Kosik, K. S. (1997). Neurotrophin-3 signals redistribute RNA in�neurons. Proc. Natl. Acad. Sci. USA 94: 14804-14808 [Abstract] [Full Text]
Kaech, S., Fischer, M., Doll, T., Matus, A. (1997). Isoform Specificity in the Relationship of Actin to Dendritic Spines. J. Neurosci. 17: 9565-9572 [Abstract] [Full Text]
Ainger, K., Avossa, D., Diana, A. S., Barry, C., Barbarese, E., Carson, J. H. (1997). Transport and Localization Elements in Myelin Basic Protein mRNA. JCB 138: 1077-1087 [Abstract] [Full Text]
Kislauskis, E. H., Zhu, X.-c., Singer, R. H. (1997). {beta}-Actin Messenger RNA Localization and Protein Synthesis Augment Cell Motility. JCB 136: 1263-1270 [Abstract] [Full Text]
Gautreau, D, Cote, C., Mowry, K. (1997). Two copies of a subelement from the Vg1 RNA localization sequence are sufficient to direct vegetal localization in Xenopus oocytes. Development 124: 5013-5020 [Abstract]
Mounier, N, Perriard, J., Gabbiani, G, Chaponnier, C (1997). Transfected muscle and non-muscle actins are differentially sorted by cultured smooth muscle and non-muscle cells. J. Cell Sci. 110: 839-846 [Abstract]
Guenal, I, Risler, Y, Mignotte, B (1997). Down-regulation of actin genes precedes microfilament network disruption and actin cleavage during p53-mediated apoptosis. J. Cell Sci. 110: 489-495 [Abstract]
Feres-Filho, E. J., Menassa, G. B., Trackman, P. C. (1996). Regulation of Lysyl Oxidase by Basic Fibroblast Growth Factor in Osteoblastic MC3T3-E1 Cells. J. Biol. Chem. 271: 6411-6416 [Abstract] [Full Text]
Margot, J. B., Williams, D. L. (1996). Estrogen Induces the Assembly of a Multiprotein Messenger Ribonucleoprotein Complex on the 3`-Untranslated Region of Chicken Apolipoprotein II mRNA. J. Biol. Chem. 271: 4452-4460 [Abstract] [Full Text]
Edmonds, B., Wyckoff, J, Yeung, Y., Wang, Y, Stanley, E., Jones, J, Segall, J, Condeelis, J (1996). Elongation factor-1 alpha is an overexpressed actin binding protein in metastatic rat mammary adenocarcinoma. J. Cell Sci. 109: 2705-2714 [Abstract]
Zhou, Y, King, M. (1996). Localization of Xcat-2 RNA, a putative germ plasm component, to the mitochondrial cloud in Xenopus stage I oocytes. Development 122: 2947-2953 [Abstract]
Veyrune, J., Campbell, G., Wiseman, J, Blanchard, J., Hesketh, J. (1996). A localisation signal in the 3' untranslated region of c-myc mRNA targets c-myc mRNA and beta-globin reporter sequences to the perinuclear cytoplasm and cytoskeletal-bound polysomes. J. Cell Sci. 109: 1185-1194 [Abstract]
Dalgleish, G., Veyrune, J.-L., Blanchard, J.-M., Hesketh, J. (2001). mRNA Localization by a 145-Nucleotide Region of the c-fos 3'- Untranslated Region. LINKS TO TRANSLATION BUT NOT STABILITY. J. Biol. Chem. 276: 13593-13599 [Abstract] [Full Text]
Wong, P. M. C., Yuan, Q., Chen, H., Sultzer, B. M., Chung, S.-W. (2001). A Single Point Mutation at the 3'-Untranslated Region of Ran mRNA Leads to Profound Changes in Lipopolysaccharide Endotoxin-mediated Responses. J. Biol. Chem. 276: 33129-33138 [Abstract] [Full Text]
Gramolini, A. O., Belanger, G., Jasmin, B. J. (2001). Distinct regions in the 3' untranslated region are responsible for targeting and stabilizing utrophin transcripts in skeletal muscle cells. JCB 154: 1173-1184 [Abstract] [Full Text]
van Eeden, F. J.M., Palacios, I. M., Petronczki, M., Weston, M. J.D., St Johnston, D. (2001). Barentsz is essential for the posterior localization of oskar mRNA and colocalizes with it to the posterior pole. JCB 154: 511-524 [Abstract] [Full Text]
Gu, W., Pan, F., Zhang, H., Bassell, G. J., Singer, R. H. (2002). A predominantly nuclear protein affecting cytoplasmic localization of {beta}-actin mRNA in fibroblasts and neurons. JCB 156: 41-52 [Abstract] [Full Text]
Liu, G., Grant, W. M., Persky, D., Latham, V. M. Jr., Singer, R. H., Condeelis, J. (2002). Interactions of Elongation Factor 1alpha with F-Actin and beta -Actin mRNA: Implications for Anchoring mRNA in Cell Protrusions. Mol. Biol. Cell 13: 579-592 [Abstract] [Full Text]