Skip to main content
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1995 Aug 1;92(16):7520–7524. doi: 10.1073/pnas.92.16.7520

Transdifferentiation of chicken embryonic cells into muscle cells by the 3' untranslated region of muscle tropomyosin.

T J L'Ecuyer 1, P C Tompach 1, E Morris 1, A B Fulton 1
PMCID: PMC41371  PMID: 7638223

Abstract

Transfection with a plasmid encoding the 3' untranslated region (3' UTR) of skeletal muscle tropomyosin induces chicken embryonic fibroblasts to express skeletal tropomyosin. Such cells become spindle shaped, fuse, and express titin, a marker of striated muscle differentiation. Skeletal muscle tropomyosin and titin organize in sarcomeric arrays. When the tropomyosin 3' UTR is expressed in osteoblasts, less skeletal muscle tropomyosin is expressed, and titin expression is delayed. Some transfected osteoblasts become spindle shaped but do not fuse nor organize these proteins into sarcomeres. Transfected cells expressing muscle tropomyosin organize muscle and nonmuscle isoforms into the same structures. Thus, the skeletal muscle tropomyosin 3' UTR induces transdifferentiation into a striated muscle phenotype in a cell-type-specific context.

Full text

PDF
7520

Images in this article

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Andersson S., Davis D. L., Dahlbäck H., Jörnvall H., Russell D. W. Cloning, structure, and expression of the mitochondrial cytochrome P-450 sterol 26-hydroxylase, a bile acid biosynthetic enzyme. J Biol Chem. 1989 May 15;264(14):8222–8229. [PubMed] [Google Scholar]
  2. Bachem M. G., Meyer D., Schäfer W., Riess U., Melchior R., Sell K. M., Gressner A. M. The response of rat liver perisinusoidal lipocytes to polypeptide growth regulator changes with their transdifferentiation into myofibroblast-like cells in culture. J Hepatol. 1993 Apr;18(1):40–52. doi: 10.1016/s0168-8278(05)80008-x. [DOI] [PubMed] [Google Scholar]
  3. Bachem M. G., Sell K. M., Melchior R., Kropf J., Eller T., Gressner A. M. Tumor necrosis factor alpha (TNF alpha) and transforming growth factor beta 1 (TGF beta 1) stimulate fibronectin synthesis and the transdifferentiation of fat-storing cells in the rat liver into myofibroblasts. Virchows Arch B Cell Pathol Incl Mol Pathol. 1993;63(2):123–130. doi: 10.1007/BF02899251. [DOI] [PubMed] [Google Scholar]
  4. Bagby G. C., Shaw G., Heinrich M. C., Hefeneider S., Brown M. A., DeLoughery T. G., Segal G. M., Band L. Interleukin-1 stimulation stabilizes GM-CSF mRNA in human vascular endothelial cells: preliminary studies on the role of the 3' AU rich motif. Prog Clin Biol Res. 1990;352:233–239. [PubMed] [Google Scholar]
  5. Beresford W. A. Direct transdifferentiation: can cells change their phenotype without dividing? Cell Differ Dev. 1990 Feb;29(2):81–93. doi: 10.1016/0922-3371(90)90026-s. [DOI] [PubMed] [Google Scholar]
  6. Berry M. J., Banu L., Harney J. W., Larsen P. R. Functional characterization of the eukaryotic SECIS elements which direct selenocysteine insertion at UGA codons. EMBO J. 1993 Aug;12(8):3315–3322. doi: 10.1002/j.1460-2075.1993.tb06001.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Bickel M., Iwai Y., Pluznik D. H., Cohen R. B. Binding of sequence-specific proteins to the adenosine- plus uridine-rich sequences of the murine granulocyte/macrophage colony-stimulating factor mRNA. Proc Natl Acad Sci U S A. 1992 Nov 1;89(21):10001–10005. doi: 10.1073/pnas.89.21.10001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Blowers A. D., Klein U., Ellmore G. S., Bogorad L. Functional in vivo analyses of the 3' flanking sequences of the Chlamydomonas chloroplast rbcL and psaB genes. Mol Gen Genet. 1993 Apr;238(3):339–349. doi: 10.1007/BF00291992. [DOI] [PubMed] [Google Scholar]
  9. Brown B. D., Zipkin I. D., Harland R. M. Sequence-specific endonucleolytic cleavage and protection of mRNA in Xenopus and Drosophila. Genes Dev. 1993 Aug;7(8):1620–1631. doi: 10.1101/gad.7.8.1620. [DOI] [PubMed] [Google Scholar]
  10. Chen C. Y., Chen T. M., Shyu A. B. Interplay of two functionally and structurally distinct domains of the c-fos AU-rich element specifies its mRNA-destabilizing function. Mol Cell Biol. 1994 Jan;14(1):416–426. doi: 10.1128/mcb.14.1.416. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Cho Y. J., Liu J., Hitchcock-DeGregori S. E. The amino terminus of muscle tropomyosin is a major determinant for function. J Biol Chem. 1990 Jan 5;265(1):538–545. [PubMed] [Google Scholar]
  12. Choi J., Costa M. L., Mermelstein C. S., Chagas C., Holtzer S., Holtzer H. MyoD converts primary dermal fibroblasts, chondroblasts, smooth muscle, and retinal pigmented epithelial cells into striated mononucleated myoblasts and multinucleated myotubes. Proc Natl Acad Sci U S A. 1990 Oct;87(20):7988–7992. doi: 10.1073/pnas.87.20.7988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Cripe L., Morris E., Fulton A. B. Vimentin mRNA location changes during muscle development. Proc Natl Acad Sci U S A. 1993 Apr 1;90(7):2724–2728. doi: 10.1073/pnas.90.7.2724. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Dix D. J., Lin P. N., McKenzie A. R., Walden W. E., Theil E. C. The influence of the base-paired flanking region on structure and function of the ferritin mRNA iron regulatory element. J Mol Biol. 1993 May 20;231(2):230–240. doi: 10.1006/jmbi.1993.1278. [DOI] [PubMed] [Google Scholar]
  15. Eguchi G., Kodama R. Transdifferentiation. Curr Opin Cell Biol. 1993 Dec;5(6):1023–1028. doi: 10.1016/0955-0674(93)90087-7. [DOI] [PubMed] [Google Scholar]
  16. Emery-Goodman A., Hirling H., Scarpellino L., Henderson B., Kühn L. C. Iron regulatory factor expressed from recombinant baculovirus: conversion between the RNA-binding apoprotein and Fe-S cluster containing aconitase. Nucleic Acids Res. 1993 Mar 25;21(6):1457–1461. doi: 10.1093/nar/21.6.1457. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Fulton A. B., L'Ecuyer T. Cotranslational assembly of some cytoskeletal proteins: implications and prospects. J Cell Sci. 1993 Aug;105(Pt 4):867–871. doi: 10.1242/jcs.105.4.867. [DOI] [PubMed] [Google Scholar]
  18. Fyrberg C. C., Labeit S., Bullard B., Leonard K., Fyrberg E. Drosophila projectin: relatedness to titin and twitchin and correlation with lethal(4) 102 CDa and bent-dominant mutants. Proc Biol Sci. 1992 Jul 22;249(1324):33–40. doi: 10.1098/rspb.1992.0080. [DOI] [PubMed] [Google Scholar]
  19. Gallie D. R., Walbot V. RNA pseudoknot domain of tobacco mosaic virus can functionally substitute for a poly(A) tail in plant and animal cells. Genes Dev. 1990 Jul;4(7):1149–1157. doi: 10.1101/gad.4.7.1149. [DOI] [PubMed] [Google Scholar]
  20. Gorospe M., Baglioni C. Degradation of unstable interleukin-1 alpha mRNA in a rabbit reticulocyte cell-free system. Localization of an instability determinant to a cluster of AUUUA motifs. J Biol Chem. 1994 Apr 22;269(16):11845–11851. [PubMed] [Google Scholar]
  21. Greenberg M. E., Shyu A. B., Belasco J. G. Deadenylylation: a mechanism controlling c-fos mRNA decay. Enzyme. 1990;44(1-4):181–192. doi: 10.1159/000468756. [DOI] [PubMed] [Google Scholar]
  22. Hall P. A., Lemoine N. R. Rapid acinar to ductal transdifferentiation in cultured human exocrine pancreas. J Pathol. 1992 Feb;166(2):97–103. doi: 10.1002/path.1711660203. [DOI] [PubMed] [Google Scholar]
  23. Hansen L. K., Mooney D. J., Vacanti J. P., Ingber D. E. Integrin binding and cell spreading on extracellular matrix act at different points in the cell cycle to promote hepatocyte growth. Mol Biol Cell. 1994 Sep;5(9):967–975. doi: 10.1091/mbc.5.9.967. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Herrick D. J., Ross J. The half-life of c-myc mRNA in growing and serum-stimulated cells: influence of the coding and 3' untranslated regions and role of ribosome translocation. Mol Cell Biol. 1994 Mar;14(3):2119–2128. doi: 10.1128/mcb.14.3.2119. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Isaacs W. B., Cook R. K., Van Atta J. C., Redmond C. M., Fulton A. B. Assembly of vimentin in cultured cells varies with cell type. J Biol Chem. 1989 Oct 25;264(30):17953–17960. [PubMed] [Google Scholar]
  26. Isaacs W. B., Kim I. S., Struve A., Fulton A. B. Biosynthesis of titin in cultured skeletal muscle cells. J Cell Biol. 1989 Nov;109(5):2189–2195. doi: 10.1083/jcb.109.5.2189. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Kennedy I. M., Haddow J. K., Clements J. B. A negative regulatory element in the human papillomavirus type 16 genome acts at the level of late mRNA stability. J Virol. 1991 Apr;65(4):2093–2097. doi: 10.1128/jvi.65.4.2093-2097.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Kislauskis E. H., Li Z., Singer R. H., Taneja K. L. Isoform-specific 3'-untranslated sequences sort alpha-cardiac and beta-cytoplasmic actin messenger RNAs to different cytoplasmic compartments. J Cell Biol. 1993 Oct;123(1):165–172. doi: 10.1083/jcb.123.1.165. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Kosaka J., Watanabe K., Eguchi G. Transdifferentiation of chicken retinal pigmented epithelial cells in serum-free culture. Exp Eye Res. 1992 Aug;55(2):261–267. doi: 10.1016/0014-4835(92)90190-4. [DOI] [PubMed] [Google Scholar]
  30. Laird-Offringa I. A. What determines the instability of c-myc proto-oncogene mRNA? Bioessays. 1992 Feb;14(2):119–124. doi: 10.1002/bies.950140209. [DOI] [PubMed] [Google Scholar]
  31. Leathers V., Tanguay R., Kobayashi M., Gallie D. R. A phylogenetically conserved sequence within viral 3' untranslated RNA pseudoknots regulates translation. Mol Cell Biol. 1993 Sep;13(9):5331–5347. doi: 10.1128/mcb.13.9.5331. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Lin J. J., Chou C. S., Lin J. L. Monoclonal antibodies against chicken tropomyosin isoforms: production, characterization, and application. Hybridoma. 1985 Fall;4(3):223–242. doi: 10.1089/hyb.1985.4.223. [DOI] [PubMed] [Google Scholar]
  33. Lipton B. H., Bensch K. G., Karasek M. A. Microvessel endothelial cell transdifferentiation: phenotypic characterization. Differentiation. 1991 Mar;46(2):117–133. doi: 10.1111/j.1432-0436.1991.tb00872.x. [DOI] [PubMed] [Google Scholar]
  34. Newman T. C., Ohme-Takagi M., Taylor C. B., Green P. J. DST sequences, highly conserved among plant SAUR genes, target reporter transcripts for rapid decay in tobacco. Plant Cell. 1993 Jun;5(6):701–714. doi: 10.1105/tpc.5.6.701. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Pryhuber G. S., Church S. L., Kroft T., Panchal A., Whitsett J. A. 3'-untranslated region of SP-B mRNA mediates inhibitory effects of TPA and TNF-alpha on SP-B expression. Am J Physiol. 1994 Jul;267(1 Pt 1):L16–L24. doi: 10.1152/ajplung.1994.267.1.L16. [DOI] [PubMed] [Google Scholar]
  36. Rando T. A., Blau H. M. Primary mouse myoblast purification, characterization, and transplantation for cell-mediated gene therapy. J Cell Biol. 1994 Jun;125(6):1275–1287. doi: 10.1083/jcb.125.6.1275. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Rastinejad F., Blau H. M. Genetic complementation reveals a novel regulatory role for 3' untranslated regions in growth and differentiation. Cell. 1993 Mar 26;72(6):903–917. doi: 10.1016/0092-8674(93)90579-f. [DOI] [PubMed] [Google Scholar]
  38. Rastinejad F., Conboy M. J., Rando T. A., Blau H. M. Tumor suppression by RNA from the 3' untranslated region of alpha-tropomyosin. Cell. 1993 Dec 17;75(6):1107–1117. doi: 10.1016/0092-8674(93)90320-p. [DOI] [PubMed] [Google Scholar]
  39. Rastinejad F., Conboy M. J., Rando T. A., Blau H. M. Tumor suppression by RNA from the 3' untranslated region of alpha-tropomyosin. Cell. 1993 Dec 17;75(6):1107–1117. doi: 10.1016/0092-8674(93)90320-p. [DOI] [PubMed] [Google Scholar]
  40. Schiavi S. C., Wellington C. L., Shyu A. B., Chen C. Y., Greenberg M. E., Belasco J. G. Multiple elements in the c-fos protein-coding region facilitate mRNA deadenylation and decay by a mechanism coupled to translation. J Biol Chem. 1994 Feb 4;269(5):3441–3448. [PubMed] [Google Scholar]
  41. Schmid V., Alder H., Plickert G., Weber C. Transdifferentiation from striated muscle of medusae in vitro. Cell Differ Dev. 1988 Nov;25 (Suppl):137–146. doi: 10.1016/0922-3371(88)90110-4. [DOI] [PubMed] [Google Scholar]
  42. Seeger M. A., Kaufman T. C. Molecular analysis of the bicoid gene from Drosophila pseudoobscura: identification of conserved domains within coding and noncoding regions of the bicoid mRNA. EMBO J. 1990 Sep;9(9):2977–2987. doi: 10.1002/j.1460-2075.1990.tb07490.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Sheets M. D., Fox C. A., Hunt T., Vande Woude G., Wickens M. The 3'-untranslated regions of c-mos and cyclin mRNAs stimulate translation by regulating cytoplasmic polyadenylation. Genes Dev. 1994 Apr 15;8(8):926–938. doi: 10.1101/gad.8.8.926. [DOI] [PubMed] [Google Scholar]
  44. Spirin A. S. Storage of messenger RNA in eukaryotes: envelopment with protein, translational barrier at 5' side, or conformational masking by 3' side? Mol Reprod Dev. 1994 May;38(1):107–117. doi: 10.1002/mrd.1080380117. [DOI] [PubMed] [Google Scholar]
  45. Standart N., Jackson R. J. Regulation of translation by specific protein/mRNA interactions. Biochimie. 1994;76(9):867–879. doi: 10.1016/0300-9084(94)90189-9. [DOI] [PubMed] [Google Scholar]
  46. Ueno S., Kotani Y., Kondoh K., Sano A., Kakimoto Y., Campagnoni A. T. The 3'-untranslated region of mouse myelin basic protein gene increases the amount of mRNA in immortalized mouse oligodendrocytes. Biochem Biophys Res Commun. 1994 Nov 15;204(3):1352–1357. doi: 10.1006/bbrc.1994.2612. [DOI] [PubMed] [Google Scholar]
  47. Wharton R. P., Struhl G. RNA regulatory elements mediate control of Drosophila body pattern by the posterior morphogen nanos. Cell. 1991 Nov 29;67(5):955–967. doi: 10.1016/0092-8674(91)90368-9. [DOI] [PubMed] [Google Scholar]
  48. Wormington M. Unmasking the role of the 3' UTR in the cytoplasmic polyadenylation and translational regulation of maternal mRNAs. Bioessays. 1994 Aug;16(8):533–535. doi: 10.1002/bies.950160804. [DOI] [PubMed] [Google Scholar]
  49. You Y., Chen C. Y., Shyu A. B. U-rich sequence-binding proteins (URBPs) interacting with a 20-nucleotide U-rich sequence in the 3' untranslated region of c-fos mRNA may be involved in the first step of c-fos mRNA degradation. Mol Cell Biol. 1992 Jul;12(7):2931–2940. doi: 10.1128/mcb.12.7.2931. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Zeyenko V. V., Ryabova L. A., Gallie D. R., Spirin A. S. Enhancing effect of the 3'-untranslated region of tobacco mosaic virus RNA on protein synthesis in vitro. FEBS Lett. 1994 Nov 14;354(3):271–273. doi: 10.1016/0014-5793(94)01126-5. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES