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J Virol. 1990 June; 64(6): 2669–2677.
PMCID: PMC249445

Translation by the adenovirus tripartite leader: elements which determine independence from cap-binding protein complex.

Abstract

The adenovirus tripartite leader is a 200-nucleotide-long 5' noncoding region which facilitates translation of viral mRNAs at late times after infection. The tripartite leader also confers the ability to initiate translation independent of the requirement for cap-binding protein complex or eIF-4F without any requirement for adenovirus gene products. To elucidate the manner by which the tripartite leader functions, the primary determinants of leader activity were investigated in vivo by testing a series of mutations expressed from transfected plasmids. The results of these experiments indicate that the tripartite leader does not promote internal ribosome binding, at least in a manner recently described for picornavirus mRNAs. In addition, despite an unusual arrangement of sequences complementary to the 3' end of 18S rRNA in the tripartite leader, we could find no evidence for involvement in its translation activity. Instead, our results are consistent with a model in which much of the first leader is maintained in an unstructured conformation which determines the ability of the tripartite leader to facilitate translation and bypass a normal requirement for eIF-4F activity. Several possible translation models are discussed, as well as the implications for translation of late viral mRNAs.

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Selected References

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  • Abramson RD, Dever TE, Lawson TG, Ray BK, Thach RE, Merrick WC. The ATP-dependent interaction of eukaryotic initiation factors with mRNA. J Biol Chem. 1987 Mar 15;262(8):3826–3832. [PubMed]
  • Abramson RD, Dever TE, Merrick WC. Biochemical evidence supporting a mechanism for cap-independent and internal initiation of eukaryotic mRNA. J Biol Chem. 1988 May 5;263(13):6016–6019. [PubMed]
  • Azad AA, Deacon NJ. The 3'-terminal primary structure of five eukaryotic 18S rRNAs determined by the direct chemical method of sequencing. The highly conserved sequences include an invariant region complementary to eukaryotic 5S rRNA. Nucleic Acids Res. 1980 Oct 10;8(19):4365–4376. [PMC free article] [PubMed]
  • Berkner KL, Sharp PA. Effect of the tripartite leader on synthesis of a non-viral protein in an adenovirus 5 recombinant. Nucleic Acids Res. 1985 Feb 11;13(3):841–857. [PMC free article] [PubMed]
  • Bienkowska-Szewczyk K, Ehrenfeld E. An internal 5'-noncoding region required for translation of poliovirus RNA in vitro. J Virol. 1988 Aug;62(8):3068–3072. [PMC free article] [PubMed]
  • Browning KS, Fletcher L, Ravel JM. Evidence that the requirements for ATP and wheat germ initiation factors 4A and 4F are affected by a region of satellite tobacco necrosis virus RNA that is 3' to the ribosomal binding site. J Biol Chem. 1988 Jun 15;263(17):8380–8383. [PubMed]
  • Curran J, Kolakofsky D. Scanning independent ribosomal initiation of the Sendai virus X protein. EMBO J. 1988 Sep;7(9):2869–2874. [PubMed]
  • Darveau A, Pelletier J, Sonenberg N. Differential efficiencies of in vitro translation of mouse c-myc transcripts differing in the 5' untranslated region. Proc Natl Acad Sci U S A. 1985 Apr;82(8):2315–2319. [PubMed]
  • De Benedetti A, Baglioni C. Inhibition of mRNA binding to ribosomes by localized activation of dsRNA-dependent protein kinase. Nature. 1984 Sep 6;311(5981):79–81. [PubMed]
  • De Benedetti A, Williams GJ, Baglioni C. Inhibition of binding to initiation complexes of nascent reovirus mRNA by double-stranded RNA-dependent protein kinase. J Virol. 1985 May;54(2):408–413. [PMC free article] [PubMed]
  • Dolph PJ, Racaniello V, Villamarin A, Palladino F, Schneider RJ. The adenovirus tripartite leader may eliminate the requirement for cap-binding protein complex during translation initiation. J Virol. 1988 Jun;62(6):2059–2066. [PMC free article] [PubMed]
  • Feinberg AP, Vogelstein B. A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem. 1983 Jul 1;132(1):6–13. [PubMed]
  • Gallie DR, Kado CI. A translational enhancer derived from tobacco mosaic virus is functionally equivalent to a Shine-Dalgarno sequence. Proc Natl Acad Sci U S A. 1989 Jan;86(1):129–132. [PubMed]
  • Gehrke L, Auron PE, Quigley GJ, Rich A, Sonenberg N. 5'-Conformation of capped alfalfa mosaic virus ribonucleic acid 4 may reflect its independence of the cap structure or of cap-binding protein for efficient translation. Biochemistry. 1983 Oct 25;22(22):5157–5164. [PubMed]
  • Gluzman Y. SV40-transformed simian cells support the replication of early SV40 mutants. Cell. 1981 Jan;23(1):175–182. [PubMed]
  • Gorman CM, Moffat LF, Howard BH. Recombinant genomes which express chloramphenicol acetyltransferase in mammalian cells. Mol Cell Biol. 1982 Sep;2(9):1044–1051. [PMC free article] [PubMed]
  • Guan KL, Weiner H. Influence of the 5'-end region of aldehyde dehydrogenase mRNA on translational efficiency. Potential secondary structure inhibition of translation in vitro. J Biol Chem. 1989 Oct 25;264(30):17764–17769. [PubMed]
  • Hagenbüchle O, Santer M, Steitz JA, Mans RJ. Conservation of the primary structure at the 3' end of 18S rRNA from eucaryotic cells. Cell. 1978 Mar;13(3):551–563. [PubMed]
  • Herman RC. Alternatives for the initiation of translation. Trends Biochem Sci. 1989 Jun;14(6):219–222. [PubMed]
  • Jackson RJ. RNA translation. Picornaviruses break the rules. Nature. 1988 Jul 28;334(6180):292–293. [PubMed]
  • Jang SK, Kräusslich HG, Nicklin MJ, Duke GM, Palmenberg AC, Wimmer E. A segment of the 5' nontranslated region of encephalomyocarditis virus RNA directs internal entry of ribosomes during in vitro translation. J Virol. 1988 Aug;62(8):2636–2643. [PMC free article] [PubMed]
  • Kaufman RJ. Identification of the components necessary for adenovirus translational control and their utilization in cDNA expression vectors. Proc Natl Acad Sci U S A. 1985 Feb;82(3):689–693. [PubMed]
  • Kozak M. Influence of mRNA secondary structure on binding and migration of 40S ribosomal subunits. Cell. 1980 Jan;19(1):79–90. [PubMed]
  • Kozak M. Leader length and secondary structure modulate mRNA function under conditions of stress. Mol Cell Biol. 1988 Jul;8(7):2737–2744. [PMC free article] [PubMed]
  • Kozak M. Circumstances and mechanisms of inhibition of translation by secondary structure in eucaryotic mRNAs. Mol Cell Biol. 1989 Nov;9(11):5134–5142. [PMC free article] [PubMed]
  • Kunkel TA. Rapid and efficient site-specific mutagenesis without phenotypic selection. Proc Natl Acad Sci U S A. 1985 Jan;82(2):488–492. [PubMed]
  • Lawson TG, Ray BK, Dodds JT, Grifo JA, Abramson RD, Merrick WC, Betsch DF, Weith HL, Thach RE. Influence of 5' proximal secondary structure on the translational efficiency of eukaryotic mRNAs and on their interaction with initiation factors. J Biol Chem. 1986 Oct 25;261(30):13979–13989. [PubMed]
  • Lewis ED, Manley JL. Control of adenovirus late promoter expression in two human cell lines. Mol Cell Biol. 1985 Sep;5(9):2433–2442. [PMC free article] [PubMed]
  • Lingelbach K, Dobberstein B. An extended RNA/RNA duplex structure within the coding region of mRNA does not block translational elongation. Nucleic Acids Res. 1988 Apr 25;16(8):3405–3414. [PMC free article] [PubMed]
  • Logan J, Shenk T. Adenovirus tripartite leader sequence enhances translation of mRNAs late after infection. Proc Natl Acad Sci U S A. 1984 Jun;81(12):3655–3659. [PubMed]
  • Lopata MA, Cleveland DW, Sollner-Webb B. High level transient expression of a chloramphenicol acetyl transferase gene by DEAE-dextran mediated DNA transfection coupled with a dimethyl sulfoxide or glycerol shock treatment. Nucleic Acids Res. 1984 Jul 25;12(14):5707–5717. [PMC free article] [PubMed]
  • Mathews MB. Binding of adenovirus VA RNA to mRNA: a possible role in splicing? Nature. 1980 Jun 19;285(5766):575–577. [PubMed]
  • Muñoz A, Alonso MA, Carrasco L. Synthesis of heat-shock proteins in HeLa cells: inhibition by virus infection. Virology. 1984 Aug;137(1):150–159. [PubMed]
  • Nakashima K, Darzynkiewicz E, Shatkin AJ. Proximity of mRNA5'-region and 18S rRNA in eukaryotic initiation complexes. Nature. 1980 Jul 17;286(5770):226–230. [PubMed]
  • Pelletier J, Sonenberg N. Insertion mutagenesis to increase secondary structure within the 5' noncoding region of a eukaryotic mRNA reduces translational efficiency. Cell. 1985 Mar;40(3):515–526. [PubMed]
  • Pelletier J, Sonenberg N. Internal initiation of translation of eukaryotic mRNA directed by a sequence derived from poliovirus RNA. Nature. 1988 Jul 28;334(6180):320–325. [PubMed]
  • Ray BK, Lawson TG, Kramer JC, Cladaras MH, Grifo JA, Abramson RD, Merrick WC, Thach RE. ATP-dependent unwinding of messenger RNA structure by eukaryotic initiation factors. J Biol Chem. 1985 Jun 25;260(12):7651–7658. [PubMed]
  • Samuel CE. Mechanism of interferon action: phosphorylation of protein synthesis initiation factor eIF-2 in interferon-treated human cells by a ribosome-associated kinase processing site specificity similar to hemin-regulated rabbit reticulocyte kinase. Proc Natl Acad Sci U S A. 1979 Feb;76(2):600–604. [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. [PubMed]
  • Sarnow P. Translation of glucose-regulated protein 78/immunoglobulin heavy-chain binding protein mRNA is increased in poliovirus-infected cells at a time when cap-dependent translation of cellular mRNAs is inhibited. Proc Natl Acad Sci U S A. 1989 Aug;86(15):5795–5799. [PubMed]
  • Schneider RJ, Safer B, Munemitsu SM, Samuel CE, Shenk T. Adenovirus VAI RNA prevents phosphorylation of the eukaryotic initiation factor 2 alpha subunit subsequent to infection. Proc Natl Acad Sci U S A. 1985 Jul;82(13):4321–4325. [PubMed]
  • Shatkin AJ. mRNA cap binding proteins: essential factors for initiating translation. Cell. 1985 Feb;40(2):223–224. [PubMed]
  • Siekierka J, Mariano TM, Reichel PA, Mathews MB. Translational control by adenovirus: lack of virus-associated RNAI during adenovirus infection results in phosphorylation of initiation factor eIF-2 and inhibition of protein synthesis. Proc Natl Acad Sci U S A. 1985 Apr;82(7):1959–1963. [PubMed]
  • Spena A, Krause E, Dobberstein B. Translation efficiency of zein mRNA is reduced by hybrid formation between the 5'- and 3'-untranslated region. EMBO J. 1985 Sep;4(9):2153–2158. [PubMed]
  • Thomas PS. Hybridization of denatured RNA and small DNA fragments transferred to nitrocellulose. Proc Natl Acad Sci U S A. 1980 Sep;77(9):5201–5205. [PubMed]
  • Zhang Y, Dolph PJ, Schneider RJ. Secondary structure analysis of adenovirus tripartite leader. J Biol Chem. 1989 Jun 25;264(18):10679–10684. [PubMed]

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