• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of narLink to Publisher's site
Nucleic Acids Res. Mar 1, 1997; 25(5): 995–1001.
PMCID: PMC146534

The 5' terminal oligopyrimidine tract confers translational control on TOP mRNAs in a cell type- and sequence context-dependent manner.

Abstract

TOP mRNAs are vertebrate transcripts which contain a 5'terminal oligopyrimidine tract (5'TOP), encode for ribosomal proteins and elongation factors 1alpha and 2, and are candidates for growth-dependent translational control mediated through their 5'TOP. In the present study we show that elongation factor 2 (EF2) mRNA is translationally regulated in a growth-dependent manner in cells of hematopoietic origin, but not in any of three different non-hematopoietic cell lines studied. Human beta1-tubulin mRNA is a new member of the family which contains all the hallmarks of a typical TOP mRNA, yet its translation is refractory to growth arrest of any of the examined cell lines. Transfection experiments indicate that the first 29 and 53 nucleotides of the mRNAs encoding EF2 and beta1-tubulin, respectively, contain all the translational cis-regulatory elements sufficient for ubiquitously conferring growth-dependent translational control on a reporter mRNA. These results suggest that the distinct translational regulation of TOP mRNAs reflects downstream sequences which can override the regulatory features of the 5'TOP in a cell type-specific manner. This notion is further supported by the fact that mutations within the region immediately downstream of the 5'TOP of rpS16 mRNA confer onto the resulting transcripts growth-dependent translational control with a cell type specificity similar to that displayed by EF2 mRNA.

Full Text

The Full Text of this article is available as a PDF (197K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Jefferies HB, Reinhard C, Kozma SC, Thomas G. Rapamycin selectively represses translation of the "polypyrimidine tract" mRNA family. Proc Natl Acad Sci U S A. 1994 May 10;91(10):4441–4445. [PMC free article] [PubMed]
  • Terada N, Patel HR, Takase K, Kohno K, Nairn AC, Gelfand EW. Rapamycin selectively inhibits translation of mRNAs encoding elongation factors and ribosomal proteins. Proc Natl Acad Sci U S A. 1994 Nov 22;91(24):11477–11481. [PMC free article] [PubMed]
  • Uetsuki T, Naito A, Nagata S, Kaziro Y. Isolation and characterization of the human chromosomal gene for polypeptide chain elongation factor-1 alpha. J Biol Chem. 1989 Apr 5;264(10):5791–5798. [PubMed]
  • Nakanishi T, Kohno K, Ishiura M, Ohashi H, Uchida T. Complete nucleotide sequence and characterization of the 5'-flanking region of mammalian elongation factor 2 gene. J Biol Chem. 1988 May 5;263(13):6384–6391. [PubMed]
  • Levy S, Avni D, Hariharan N, Perry RP, Meyuhas O. Oligopyrimidine tract at the 5' end of mammalian ribosomal protein mRNAs is required for their translational control. Proc Natl Acad Sci U S A. 1991 Apr 15;88(8):3319–3323. [PMC free article] [PubMed]
  • Avni D, Shama S, Loreni F, Meyuhas O. Vertebrate mRNAs with a 5'-terminal pyrimidine tract are candidates for translational repression in quiescent cells: characterization of the translational cis-regulatory element. Mol Cell Biol. 1994 Jun;14(6):3822–3833. [PMC free article] [PubMed]
  • Terada N, Takase K, Papst P, Nairn AC, Gelfand EW. Rapamycin inhibits ribosomal protein synthesis and induces G1 prolongation in mitogen-activated T lymphocytes. J Immunol. 1995 Oct 1;155(7):3418–3426. [PubMed]
  • Lee MG, Lewis SA, Wilde CD, Cowan NJ. Evolutionary history of a multigene family: an expressed human beta-tubulin gene and three processed pseudogenes. Cell. 1983 Jun;33(2):477–487. [PubMed]
  • Shama S, Avni D, Frederickson RM, Sonenberg N, Meyuhas O. Overexpression of initiation factor eIF-4E does not relieve the translational repression of ribosomal protein mRNAs in quiescent cells. Gene Expr. 1995;4(4-5):241–252. [PubMed]
  • Graham FL, Smiley J, Russell WC, Nairn R. Characteristics of a human cell line transformed by DNA from human adenovirus type 5. J Gen Virol. 1977 Jul;36(1):59–74. [PubMed]
  • Sanger F, Nicklen S, Coulson AR. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. [PMC free article] [PubMed]
  • Schibler U, Marcu KB, Perry RP. The synthesis and processing of the messenger RNAs specifying heavy and light chain immunoglobulins in MPC-11 cells. Cell. 1978 Dec;15(4):1495–1509. [PubMed]
  • Meyuhas O, Thompson EA, Jr, Perry RP. Glucocorticoids selectively inhibit translation of ribosomal protein mRNAs in P1798 lymphosarcoma cells. Mol Cell Biol. 1987 Aug;7(8):2691–2699. [PMC free article] [PubMed]
  • Selden RF, Howie KB, Rowe ME, Goodman HM, Moore DD. Human growth hormone as a reporter gene in regulation studies employing transient gene expression. Mol Cell Biol. 1986 Sep;6(9):3173–3179. [PMC free article] [PubMed]
  • Hariharan N, Perry RP. A characterization of the elements comprising the promoter of the mouse ribosomal protein gene RPS16. Nucleic Acids Res. 1989 Jul 11;17(13):5323–5337. [PMC free article] [PubMed]
  • Minty AJ, Caravatti M, Robert B, Cohen A, Daubas P, Weydert A, Gros F, Buckingham ME. Mouse actin messenger RNAs. Construction and characterization of a recombinant plasmid molecule containing a complementary DNA transcript of mouse alpha-actin mRNA. J Biol Chem. 1981 Jan 25;256(2):1008–1014. [PubMed]
  • Hanes J, Freudenstein J, Rapp G, Scheit KH. Construction of a plasmid containing the complete coding region of human elongation factor 2. Biol Chem Hoppe Seyler. 1992 Apr;373(4):201–204. [PubMed]
  • Chung S, Perry RP. Importance of introns for expression of mouse ribosomal protein gene rpL32. Mol Cell Biol. 1989 May;9(5):2075–2082. [PMC free article] [PubMed]
  • Wiedemann LM, Perry RP. Characterization of the expressed gene and several processed pseudogenes for the mouse ribosomal protein L30 gene family. Mol Cell Biol. 1984 Nov;4(11):2518–2528. [PMC free article] [PubMed]
  • Meyuhas O, Perry RP. Construction and identification of cDNA clones for mouse ribosomal proteins: application for the study of r-protein gene expression. Gene. 1980 Jul;10(2):113–129. [PubMed]
  • Lewis SA, Gilmartin ME, Hall JL, Cowan NJ. Three expressed sequences within the human beta-tubulin multigene family each define a distinct isotype. J Mol Biol. 1985 Mar 5;182(1):11–20. [PubMed]
  • Devi KR, Chan YL, Wool IG. The primary structure of rat ribosomal protein S4. Biochim Biophys Acta. 1989 Jul 7;1008(2):258–262. [PubMed]
  • Chan YL, Lin A, McNally J, Wool IG. The primary structure of rat ribosomal protein L5. A comparison of the sequence of amino acids in the proteins that interact with 5 S rRNA. J Biol Chem. 1987 Sep 15;262(26):12879–12886. [PubMed]
  • PUCK TT, CIECIURA SJ, ROBINSON A. Genetics of somatic mammalian cells. III. Long-term cultivation of euploid cells from human and animal subjects. J Exp Med. 1958 Dec 1;108(6):945–956. [PMC free article] [PubMed]
  • Hill JR, Morris DR. Cell-specific translation of S-adenosylmethionine decarboxylase mRNA. Regulation by the 5' transcript leader. J Biol Chem. 1992 Oct 25;267(30):21886–21893. [PubMed]
  • Imataka H, Nakayama K, Yasumoto K, Mizuno A, Fujii-Kuriyama Y, Hayami M. Cell-specific translational control of transcription factor BTEB expression. The role of an upstream AUG in the 5'-untranslated region. J Biol Chem. 1994 Aug 12;269(32):20668–20673. [PubMed]
  • Zimmer A, Zimmer AM, Reynolds K. Tissue specific expression of the retinoic acid receptor-beta 2: regulation by short open reading frames in the 5'-noncoding region. J Cell Biol. 1994 Nov;127(4):1111–1119. [PMC free article] [PubMed]
  • Ranganathan G, Ong JM, Yukht A, Saghizadeh M, Simsolo RB, Pauer A, Kern PA. Tissue-specific expression of human lipoprotein lipase. Effect of the 3'-untranslated region on translation. J Biol Chem. 1995 Mar 31;270(13):7149–7155. [PubMed]
  • Redpath NT, Foulstone EJ, Proud CG. Regulation of translation elongation factor-2 by insulin via a rapamycin-sensitive signalling pathway. EMBO J. 1996 May 1;15(9):2291–2297. [PMC free article] [PubMed]
  • Kaspar RL, Kakegawa T, Cranston H, Morris DR, White MW. A regulatory cis element and a specific binding factor involved in the mitogenic control of murine ribosomal protein L32 translation. J Biol Chem. 1992 Jan 5;267(1):508–514. [PubMed]
  • Severson WE, Mascolo PL, White MW. Lymphocyte p56L32 is a RNA/DNA-binding protein which interacts with conserved elements of the murine L32 ribosomal protein mRNA. Eur J Biochem. 1995 Apr 15;229(2):426–432. [PubMed]
  • Cardinali B, Di Cristina M, Pierandrei-Amaldi P. Interaction of proteins with the mRNA for ribosomal protein L1 in Xenopus: structural characterization of in vivo complexes and identification of proteins that bind in vitro to its 5'UTR. Nucleic Acids Res. 1993 May 25;21(10):2301–2308. [PMC free article] [PubMed]
  • Pellizzoni L, Cardinali B, Lin-Marq N, Mercanti D, Pierandrei-Amaldi P. A Xenopus laevis homologue of the La autoantigen binds the pyrimidine tract of the 5' UTR of ribosomal protein mRNAs in vitro: implication of a protein factor in complex formation. J Mol Biol. 1996 Jun 28;259(5):904–915. [PubMed]
  • Slobin LI, Rao MN. Translational repression of EF-1 alpha mRNA in vitro. Eur J Biochem. 1993 May 1;213(3):919–926. [PubMed]
  • Levanon D, Lieman-Hurwitz J, Dafni N, Wigderson M, Sherman L, Bernstein Y, Laver-Rudich Z, Danciger E, Stein O, Groner Y. Architecture and anatomy of the chromosomal locus in human chromosome 21 encoding the Cu/Zn superoxide dismutase. EMBO J. 1985 Jan;4(1):77–84. [PMC free article] [PubMed]
  • Zinn AR, Alagappan RK, Brown LG, Wool I, Page DC. Structure and function of ribosomal protein S4 genes on the human and mouse sex chromosomes. Mol Cell Biol. 1994 Apr;14(4):2485–2492. [PMC free article] [PubMed]

Articles from Nucleic Acids Research are provided here courtesy of Oxford University Press

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

  • Compound
    Compound
    PubChem Compound links
  • MedGen
    MedGen
    Related information in MedGen
  • PubMed
    PubMed
    PubMed citations for these articles
  • Substance
    Substance
    PubChem Substance links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...