Abstract
Translational initiation of encephalomyocarditis virus (EMCV) mRNA occurs by ribosomal entry into the 5' nontranslated region of the EMCV mRNA, rather than by ribosomal scanning. Internal ribosomal binding requires a cis-acting element termed the internal ribosomal entry site (IRES). IRES elements have been proposed to be involved in the translation of picornavirus mRNAs and some cellular mRNAs. Internal ribosome binding likely requires the interaction of trans-acting factors that recognize both the mRNA and the ribosomal complex. Five cellular proteins (p52, p57, p70, p72, and p100) cross-link the EMCV IRES or fragments of the IRES. For one of these proteins, p57, binding to the IRES correlates with translation. Recently, p57 was identified to be very similar, if not identical, to polypyrimidine tract-binding protein. On the basis of cross-linking results with 21 different EMCV IRES fragments and cytoplasmic HeLa extract or rabbit reticulocyte lysate as the source of polypeptides, consensus binding sites for p52, p57, p70, and p100 are proposed. It is suggested that each of these proteins recognizes primarily a structural feature of the RNA rather than a specific sequence.
Full text
PDFImages in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Bartel D. P., Zapp M. L., Green M. R., Szostak J. W. HIV-1 Rev regulation involves recognition of non-Watson-Crick base pairs in viral RNA. Cell. 1991 Nov 1;67(3):529–536. doi: 10.1016/0092-8674(91)90527-6. [DOI] [PubMed] [Google Scholar]
- Beckett D., Wu H. N., Uhlenbeck O. C. Roles of operator and non-operator RNA sequences in bacteriophage R17 capsid assembly. J Mol Biol. 1988 Dec 20;204(4):939–947. doi: 10.1016/0022-2836(88)90053-8. [DOI] [PubMed] [Google Scholar]
- Bhattacharyya A., Murchie A. I., Lilley D. M. RNA bulges and the helical periodicity of double-stranded RNA. Nature. 1990 Feb 1;343(6257):484–487. doi: 10.1038/343484a0. [DOI] [PubMed] [Google Scholar]
- Borman A., Howell M. T., Patton J. G., Jackson R. J. The involvement of a spliceosome component in internal initiation of human rhinovirus RNA translation. J Gen Virol. 1993 Sep;74(Pt 9):1775–1788. doi: 10.1099/0022-1317-74-9-1775. [DOI] [PubMed] [Google Scholar]
- Borovjagin A. V., Ezrokhi M. V., Rostapshov V. M., Ugarova TYu, Bystrova T. F., Shatsky I. N. RNA--protein interactions within the internal translation initiation region of encephalomyocarditis virus RNA. Nucleic Acids Res. 1991 Sep 25;19(18):4999–5005. doi: 10.1093/nar/19.18.4999. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Brown E. A., Day S. P., Jansen R. W., Lemon S. M. The 5' nontranslated region of hepatitis A virus RNA: secondary structure and elements required for translation in vitro. J Virol. 1991 Nov;65(11):5828–5838. doi: 10.1128/jvi.65.11.5828-5838.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Climie S. C., Friesen J. D. Feedback regulation of the rplJL-rpoBC ribosomal protein operon of Escherichia coli requires a region of mRNA secondary structure. J Mol Biol. 1987 Dec 5;198(3):371–381. doi: 10.1016/0022-2836(87)90287-7. [DOI] [PubMed] [Google Scholar]
- Dildine S. L., Semler B. L. Conservation of RNA-protein interactions among picornaviruses. J Virol. 1992 Jul;66(7):4364–4376. doi: 10.1128/jvi.66.7.4364-4376.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dingwall C., Ernberg I., Gait M. J., Green S. M., Heaphy S., Karn J., Lowe A. D., Singh M., Skinner M. A. HIV-1 tat protein stimulates transcription by binding to a U-rich bulge in the stem of the TAR RNA structure. EMBO J. 1990 Dec;9(12):4145–4153. doi: 10.1002/j.1460-2075.1990.tb07637.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Duke G. M., Hoffman M. A., Palmenberg A. C. Sequence and structural elements that contribute to efficient encephalomyocarditis virus RNA translation. J Virol. 1992 Mar;66(3):1602–1609. doi: 10.1128/jvi.66.3.1602-1609.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Francoeur A. M., Mathews M. B. Interaction between VA RNA and the lupus antigen La: formation of a ribonucleoprotein particle in vitro. Proc Natl Acad Sci U S A. 1982 Nov;79(22):6772–6776. doi: 10.1073/pnas.79.22.6772. [DOI] [PMC free article] [PubMed] [Google Scholar]
- García-Blanco M. A., Jamison S. F., Sharp P. A. Identification and purification of a 62,000-dalton protein that binds specifically to the polypyrimidine tract of introns. Genes Dev. 1989 Dec;3(12A):1874–1886. doi: 10.1101/gad.3.12a.1874. [DOI] [PubMed] [Google Scholar]
- Ghetti A., Piñol-Roma S., Michael W. M., Morandi C., Dreyfuss G. hnRNP I, the polypyrimidine tract-binding protein: distinct nuclear localization and association with hnRNAs. Nucleic Acids Res. 1992 Jul 25;20(14):3671–3678. doi: 10.1093/nar/20.14.3671. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gil A., Sharp P. A., Jamison S. F., Garcia-Blanco M. A. Characterization of cDNAs encoding the polypyrimidine tract-binding protein. Genes Dev. 1991 Jul;5(7):1224–1236. doi: 10.1101/gad.5.7.1224. [DOI] [PubMed] [Google Scholar]
- Glickman J. N., Howe J. G., Steitz J. A. Structural analyses of EBER1 and EBER2 ribonucleoprotein particles present in Epstein-Barr virus-infected cells. J Virol. 1988 Mar;62(3):902–911. doi: 10.1128/jvi.62.3.902-911.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gottlieb E., Steitz J. A. The RNA binding protein La influences both the accuracy and the efficiency of RNA polymerase III transcription in vitro. EMBO J. 1989 Mar;8(3):841–850. doi: 10.1002/j.1460-2075.1989.tb03445.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hellen C. U., Pestova T. V., Litterst M., Wimmer E. The cellular polypeptide p57 (pyrimidine tract-binding protein) binds to multiple sites in the poliovirus 5' nontranslated region. J Virol. 1994 Feb;68(2):941–950. doi: 10.1128/jvi.68.2.941-950.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hellen C. U., Witherell G. W., Schmid M., Shin S. H., Pestova T. V., Gil A., Wimmer E. A cytoplasmic 57-kDa protein that is required for translation of picornavirus RNA by internal ribosomal entry is identical to the nuclear pyrimidine tract-binding protein. Proc Natl Acad Sci U S A. 1993 Aug 15;90(16):7642–7646. doi: 10.1073/pnas.90.16.7642. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jaeger J. A., Turner D. H., Zuker M. Improved predictions of secondary structures for RNA. Proc Natl Acad Sci U S A. 1989 Oct;86(20):7706–7710. doi: 10.1073/pnas.86.20.7706. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jaeger J. A., Turner D. H., Zuker M. Predicting optimal and suboptimal secondary structure for RNA. Methods Enzymol. 1990;183:281–306. doi: 10.1016/0076-6879(90)83019-6. [DOI] [PubMed] [Google Scholar]
- Jang S. K., Davies M. V., Kaufman R. J., Wimmer E. Initiation of protein synthesis by internal entry of ribosomes into the 5' nontranslated region of encephalomyocarditis virus RNA in vivo. J Virol. 1989 Apr;63(4):1651–1660. doi: 10.1128/jvi.63.4.1651-1660.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jang S. K., Kräusslich H. G., Nicklin M. J., Duke G. M., Palmenberg A. C., 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. doi: 10.1128/jvi.62.8.2636-2643.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jang S. K., Pestova T. V., Hellen C. U., Witherell G. W., Wimmer E. Cap-independent translation of picornavirus RNAs: structure and function of the internal ribosomal entry site. Enzyme. 1990;44(1-4):292–309. doi: 10.1159/000468766. [DOI] [PubMed] [Google Scholar]
- Jang S. K., Wimmer E. Cap-independent translation of encephalomyocarditis virus RNA: structural elements of the internal ribosomal entry site and involvement of a cellular 57-kD RNA-binding protein. Genes Dev. 1990 Sep;4(9):1560–1572. doi: 10.1101/gad.4.9.1560. [DOI] [PubMed] [Google Scholar]
- Kühn R., Luz N., Beck E. Functional analysis of the internal translation initiation site of foot-and-mouth disease virus. J Virol. 1990 Oct;64(10):4625–4631. doi: 10.1128/jvi.64.10.4625-4631.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
- Lamond A. I., Konarska M. M., Grabowski P. J., Sharp P. A. Spliceosome assembly involves the binding and release of U4 small nuclear ribonucleoprotein. Proc Natl Acad Sci U S A. 1988 Jan;85(2):411–415. doi: 10.1073/pnas.85.2.411. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Le S. Y., Zuker M. Common structures of the 5' non-coding RNA in enteroviruses and rhinoviruses. Thermodynamical stability and statistical significance. J Mol Biol. 1990 Dec 5;216(3):729–741. doi: 10.1016/0022-2836(90)90395-3. [DOI] [PubMed] [Google Scholar]
- Luz N., Beck E. Interaction of a cellular 57-kilodalton protein with the internal translation initiation site of foot-and-mouth disease virus. J Virol. 1991 Dec;65(12):6486–6494. doi: 10.1128/jvi.65.12.6486-6494.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Macejak D. G., Sarnow P. Internal initiation of translation mediated by the 5' leader of a cellular mRNA. Nature. 1991 Sep 5;353(6339):90–94. doi: 10.1038/353090a0. [DOI] [PubMed] [Google Scholar]
- Meerovitch K., Pelletier J., Sonenberg N. A cellular protein that binds to the 5'-noncoding region of poliovirus RNA: implications for internal translation initiation. Genes Dev. 1989 Jul;3(7):1026–1034. doi: 10.1101/gad.3.7.1026. [DOI] [PubMed] [Google Scholar]
- Meerovitch K., Svitkin Y. V., Lee H. S., Lejbkowicz F., Kenan D. J., Chan E. K., Agol V. I., Keene J. D., Sonenberg N. La autoantigen enhances and corrects aberrant translation of poliovirus RNA in reticulocyte lysate. J Virol. 1993 Jul;67(7):3798–3807. doi: 10.1128/jvi.67.7.3798-3807.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Milligan J. F., Groebe D. R., Witherell G. W., Uhlenbeck O. C. Oligoribonucleotide synthesis using T7 RNA polymerase and synthetic DNA templates. Nucleic Acids Res. 1987 Nov 11;15(21):8783–8798. doi: 10.1093/nar/15.21.8783. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Milligan J. F., Uhlenbeck O. C. Determination of RNA-protein contacts using thiophosphate substitutions. Biochemistry. 1989 Apr 4;28(7):2849–2855. doi: 10.1021/bi00433a016. [DOI] [PubMed] [Google Scholar]
- Molla A., Jang S. K., Paul A. V., Reuer Q., Wimmer E. Cardioviral internal ribosomal entry site is functional in a genetically engineered dicistronic poliovirus. Nature. 1992 Mar 19;356(6366):255–257. doi: 10.1038/356255a0. [DOI] [PubMed] [Google Scholar]
- Molla A., Paul A. V., Wimmer E. Cell-free, de novo synthesis of poliovirus. Science. 1991 Dec 13;254(5038):1647–1651. doi: 10.1126/science.1661029. [DOI] [PubMed] [Google Scholar]
- Mulligan G. J., Guo W., Wormsley S., Helfman D. M. Polypyrimidine tract binding protein interacts with sequences involved in alternative splicing of beta-tropomyosin pre-mRNA. J Biol Chem. 1992 Dec 15;267(35):25480–25487. [PubMed] [Google Scholar]
- Nicklin M. J., Kräusslich H. G., Toyoda H., Dunn J. J., Wimmer E. Poliovirus polypeptide precursors: expression in vitro and processing by exogenous 3C and 2A proteinases. Proc Natl Acad Sci U S A. 1987 Jun;84(12):4002–4006. doi: 10.1073/pnas.84.12.4002. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nossal G. J. The molecular and cellular basis of affinity maturation in the antibody response. Cell. 1992 Jan 10;68(1):1–2. doi: 10.1016/0092-8674(92)90198-l. [DOI] [PubMed] [Google Scholar]
- Patton J. G., Mayer S. A., Tempst P., Nadal-Ginard B. Characterization and molecular cloning of polypyrimidine tract-binding protein: a component of a complex necessary for pre-mRNA splicing. Genes Dev. 1991 Jul;5(7):1237–1251. doi: 10.1101/gad.5.7.1237. [DOI] [PubMed] [Google Scholar]
- Pelletier J., Sonenberg N. Internal binding of eucaryotic ribosomes on poliovirus RNA: translation in HeLa cell extracts. J Virol. 1989 Jan;63(1):441–444. doi: 10.1128/jvi.63.1.441-444.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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. doi: 10.1038/334320a0. [DOI] [PubMed] [Google Scholar]
- Pestova T. V., Hellen C. U., Wimmer E. Translation of poliovirus RNA: role of an essential cis-acting oligopyrimidine element within the 5' nontranslated region and involvement of a cellular 57-kilodalton protein. J Virol. 1991 Nov;65(11):6194–6204. doi: 10.1128/jvi.65.11.6194-6204.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pilipenko E. V., Blinov V. M., Chernov B. K., Dmitrieva T. M., Agol V. I. Conservation of the secondary structure elements of the 5'-untranslated region of cardio- and aphthovirus RNAs. Nucleic Acids Res. 1989 Jul 25;17(14):5701–5711. doi: 10.1093/nar/17.14.5701. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pilipenko E. V., Blinov V. M., Romanova L. I., Sinyakov A. N., Maslova S. V., Agol V. I. Conserved structural domains in the 5'-untranslated region of picornaviral genomes: an analysis of the segment controlling translation and neurovirulence. Virology. 1989 Feb;168(2):201–209. doi: 10.1016/0042-6822(89)90259-6. [DOI] [PubMed] [Google Scholar]
- Raleigh E. A., Murray N. E., Revel H., Blumenthal R. M., Westaway D., Reith A. D., Rigby P. W., Elhai J., Hanahan D. McrA and McrB restriction phenotypes of some E. coli strains and implications for gene cloning. Nucleic Acids Res. 1988 Feb 25;16(4):1563–1575. doi: 10.1093/nar/16.4.1563. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Reddy R., Henning D., Tan E., Busch H. Identification of a La protein binding site in a RNA polymerase III transcript (4.5 I RNA). J Biol Chem. 1983 Jul 10;258(13):8352–8356. [PubMed] [Google Scholar]
- Rice J. A., Crothers D. M. DNA bending by the bulge defect. Biochemistry. 1989 May 16;28(10):4512–4516. doi: 10.1021/bi00436a058. [DOI] [PubMed] [Google Scholar]
- Roy S., Delling U., Chen C. H., Rosen C. A., Sonenberg N. A bulge structure in HIV-1 TAR RNA is required for Tat binding and Tat-mediated trans-activation. Genes Dev. 1990 Aug;4(8):1365–1373. doi: 10.1101/gad.4.8.1365. [DOI] [PubMed] [Google Scholar]
- Sampson J. R., Uhlenbeck O. C. Biochemical and physical characterization of an unmodified yeast phenylalanine transfer RNA transcribed in vitro. Proc Natl Acad Sci U S A. 1988 Feb;85(4):1033–1037. doi: 10.1073/pnas.85.4.1033. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schimmel P. Parameters for the molecular recognition of transfer RNAs. Biochemistry. 1989 Apr 4;28(7):2747–2759. doi: 10.1021/bi00433a001. [DOI] [PubMed] [Google Scholar]
- Tang R. S., Draper D. E. Bulge loops used to measure the helical twist of RNA in solution. Biochemistry. 1990 Jun 5;29(22):5232–5237. doi: 10.1021/bi00474a003. [DOI] [PubMed] [Google Scholar]
- Tsukiyama-Kohara K., Iizuka N., Kohara M., Nomoto A. Internal ribosome entry site within hepatitis C virus RNA. J Virol. 1992 Mar;66(3):1476–1483. doi: 10.1128/jvi.66.3.1476-1483.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Weeks K. M., Ampe C., Schultz S. C., Steitz T. A., Crothers D. M. Fragments of the HIV-1 Tat protein specifically bind TAR RNA. Science. 1990 Sep 14;249(4974):1281–1285. doi: 10.1126/science.2205002. [DOI] [PubMed] [Google Scholar]
- Weeks K. M., Crothers D. M. RNA recognition by Tat-derived peptides: interaction in the major groove? Cell. 1991 Aug 9;66(3):577–588. doi: 10.1016/0092-8674(81)90020-9. [DOI] [PubMed] [Google Scholar]
- White S. A., Draper D. E. Effects of single-base bulges on intercalator binding to small RNA and DNA hairpins and a ribosomal RNA fragment. Biochemistry. 1989 Feb 21;28(4):1892–1897. doi: 10.1021/bi00430a069. [DOI] [PubMed] [Google Scholar]
- Witherell G. W., Gil A., Wimmer E. Interaction of polypyrimidine tract binding protein with the encephalomyocarditis virus mRNA internal ribosomal entry site. Biochemistry. 1993 Aug 17;32(32):8268–8275. doi: 10.1021/bi00083a030. [DOI] [PubMed] [Google Scholar]
- Witherell G. W., Wu H. N., Uhlenbeck O. C. Cooperative binding of R17 coat protein to RNA. Biochemistry. 1990 Dec 18;29(50):11051–11057. doi: 10.1021/bi00502a006. [DOI] [PubMed] [Google Scholar]
- Woodson S. A., Crothers D. M. Conformation of a bulge-containing oligomer from a hot-spot sequence by NMR and energy minimization. Biopolymers. 1989 Jun;28(6):1149–1177. doi: 10.1002/bip.360280608. [DOI] [PubMed] [Google Scholar]
- Woodson S. A., Crothers D. M. Structural model for an oligonucleotide containing a bulged guanosine by NMR and energy minimization. Biochemistry. 1988 May 3;27(9):3130–3141. doi: 10.1021/bi00409a004. [DOI] [PubMed] [Google Scholar]
- Wu H. N., Uhlenbeck O. C. Role of a bulged A residue in a specific RNA-protein interaction. Biochemistry. 1987 Dec 15;26(25):8221–8227. doi: 10.1021/bi00399a030. [DOI] [PubMed] [Google Scholar]
- Zuker M. On finding all suboptimal foldings of an RNA molecule. Science. 1989 Apr 7;244(4900):48–52. doi: 10.1126/science.2468181. [DOI] [PubMed] [Google Scholar]