Home LiteratureArticle Details
PMID: 9848649 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Cap-independent polysomal association of natural mRNAs encoding c-myc, BiP, and eIF4G conferred by internal ribosome entry sites.

RNA (New York, N.Y.) ·Vol. 4 ·No. 12 ·1998-12-00 ·Pages 1500-13

Johannes G, Sarnow P

Abstract

Sequence elements that can function as internal ribosome entry sites (IRES) have been identified in 5' noncoding regions of certain uncapped viral and capped cellular mRNA molecules. However, it has remained largely unknown whether IRES elements are functional when located in their natural capped mRNAs. Therefore, the polysomal association and translation of several IRES-containing cellular mRNAs was tested under conditions that severely inhibited cap-dependent translation, that is, after infection with poliovirus. It was found that several known IRES-containing mRNAs, such as BiP and c-myc, were both associated with the translation apparatus and translated in infected cells when cap-dependent translation of most host-cell mRNAs was blocked, indicating that the IRES elements were functional in their natural mRNAs. Curiously, the mRNAs that encode eukaryotic initiation factor 4GI (eIF4GI) and 4GII (eIF4GII), two proteins with high identity and similar functions in the initiation of cap-dependent translation, were both associated with polysomes in infected cells. The 5'-end sequences of eIF4GI mRNA were isolated from a cDNA expression library and shown to function as an internal ribosome entry site when placed into a dicistronic mRNA. These findings suggest that eIF4G proteins can be synthesized at times when 5' cap-dependent mRNA translation is blocked, supporting the notion that eIF4G proteins are needed in both 5' cap-independent and 5' cap-dependent translational initiation mechanisms.

MeSH Terms
Amino Acid Sequence Base Sequence Carrier Proteins/genetics DNA, Complementary/genetics,isolation & purification Endoplasmic Reticulum Chaperone BiP Eukaryotic Initiation Factor-4G HeLa Cells Heat-Shock Proteins Humans Hydrolysis Molecular Chaperones/genetics Molecular Sequence Data Peptide Initiation Factors/genetics Poliomyelitis/genetics Protein Biosynthesis Proto-Oncogene Proteins c-myc/genetics RNA Caps RNA, Messenger/genetics,metabolism Ribosomes/metabolism
Chemicals
Carrier Proteins DNA, Complementary Endoplasmic Reticulum Chaperone BiP Eukaryotic Initiation Factor-4G Heat-Shock Proteins Molecular Chaperones Peptide Initiation Factors Proto-Oncogene Proteins c-myc RNA Caps RNA, Messenger
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Johannes G
Department of Microbiology and Immunology, Stanford University School of Medicine, California 94305, USA.
Sarnow P
References (56)
56 references, click to expand
  1. The eIF4G-eIF4E complex is the target for direct cleavage by the rhinovirus 2A proteinase.
    J Virol. 1996 Dec;70(12):8444-50 PMID: 8970966
  2. Homeotic gene Antennapedia mRNA contains 5'-noncoding sequences that confer translational initiation by internal ribosome binding.
    Genes Dev. 1992 Sep;6(9):1643-53 PMID: 1355457
  3. Internal ribosome entry site within hepatitis C virus RNA.
    J Virol. 1992 Mar;66(3):1476-83 PMID: 1310759
  4. Activation of the translational suppressor 4E-BP1 following infection with encephalomyocarditis virus and poliovirus.
    Proc Natl Acad Sci U S A. 1996 May 28;93(11):5578-83 PMID: 8643618
  5. Inhibition of HeLa cell protein synthesis following poliovirus infection correlates with the proteolysis of a 220,000-dalton polypeptide associated with eucaryotic initiation factor 3 and a cap binding protein complex.
    J Biol Chem. 1982 Dec 25;257(24):14806-10 PMID: 6294080
  6. Cleavage of the cap binding protein complex polypeptide p220 is not effected by the second poliovirus protease 2A.
    Virology. 1986 Apr 15;150(1):299-303 PMID: 3006342
  7. Internal initiation of translation in eukaryotes: the picornavirus paradigm and beyond.
    RNA. 1995 Dec;1(10):985-1000 PMID: 8595564
  8. Functional characterization of the internal ribosome entry site of eIF4G mRNA.
    J Biol Chem. 1998 Feb 27;273(9):5006-12 PMID: 9478948
  9. A poliovirus temperature-sensitive RNA synthesis mutant located in a noncoding region of the genome.
    Proc Natl Acad Sci U S A. 1986 Feb;83(3):571-5 PMID: 3003739
  10. C-Myc 5' untranslated region contains an internal ribosome entry segment.
    Oncogene. 1998 Jan 22;16(3):423-8 PMID: 9467968
  11. A common function for mRNA 5' and 3' ends in translation initiation in yeast.
    Genes Dev. 1995 Dec 1;9(23):2997-3007 PMID: 7498795
  12. Initiation of protein synthesis in eukaryotic cells.
    Eur J Biochem. 1996 Mar 15;236(3):747-71 PMID: 8665893
  13. Molecular structure of the human cytoplasmic beta-actin gene: interspecies homology of sequences in the introns.
    Proc Natl Acad Sci U S A. 1985 Sep;82(18):6133-7 PMID: 2994062
  14. Location of the internal ribosome entry site in the 5' non-coding region of the immunoglobulin heavy-chain binding protein (BiP) mRNA: evidence for specific RNA-protein interactions.
    Nucleic Acids Res. 1997 Jul 15;25(14):2800-7 PMID: 9207027
  15. A novel gene, spp91-1, suppresses the splicing defect and the pre-mRNA nuclear export in the prp9-1 mutant.
    EMBO J. 1992 Sep;11(9):3279-88 PMID: 1505518
  16. Purification of two picornaviral 2A proteinases: interaction with eIF-4 gamma and influence on in vitro translation.
    Biochemistry. 1993 Jul 27;32(29):7581-8 PMID: 8338854
  17. Nucleotide sequence of the human gamma cytoskeletal actin mRNA: anomalous evolution of vertebrate non-muscle actin genes.
    Nucleic Acids Res. 1986 Jul 11;14(13):5275-94 PMID: 3737401
  18. Biochemical and genetic evidence for a pseudoknot structure at the 3' terminus of the poliovirus RNA genome and its role in viral RNA amplification.
    J Virol. 1993 Jun;67(6):2961-71 PMID: 8388482
  19. Association of the yeast poly(A) tail binding protein with translation initiation factor eIF-4G.
    EMBO J. 1996 Dec 16;15(24):7168-77 PMID: 9003792
  20. 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):2636-43 PMID: 2839690
  21. PDGF2/c-sis mRNA leader contains a differentiation-linked internal ribosomal entry site (D-IRES).
    J Biol Chem. 1997 Apr 4;272(14):9356-62 PMID: 9083072
  22. Differential expression of the translocated and the untranslocated c-myc oncogene in Burkitt lymphoma.
    Science. 1983 Oct 28;222(4622):390-3 PMID: 6414084
  23. Dominant negative mutants of mammalian translation initiation factor eIF-4A define a critical role for eIF-4F in cap-dependent and cap-independent initiation of translation.
    EMBO J. 1994 Mar 1;13(5):1205-15 PMID: 8131750
  24. Translation in vitro of vesicular stomatitis virus mRNA lacking 5'-terminal 7-methylguanosine.
    Nature. 1976 Jul 1;262(5563):32-7 PMID: 180425
  25. The translation initiation factor eIF-4E binds to a common motif shared by the translation factor eIF-4 gamma and the translational repressors 4E-binding proteins.
    Mol Cell Biol. 1995 Sep;15(9):4990-7 PMID: 7651417
  26. Preferential translation of heat shock mRNAs in HeLa cells deficient in protein synthesis initiation factors eIF-4E and eIF-4 gamma.
    J Biol Chem. 1992 Oct 15;267(29):21038-43 PMID: 1400417
  27. Regulation of c-myc mRNA stability in vitro by a labile destabilizer with an essential nucleic acid component.
    Mol Cell Biol. 1989 May;9(5):1996-2006 PMID: 2747642
  28. Extreme instability of myc mRNA in normal and transformed human cells.
    Proc Natl Acad Sci U S A. 1984 Nov;81(22):7046-50 PMID: 6594679
  29. A novel functional human eukaryotic translation initiation factor 4G.
    Mol Cell Biol. 1998 Jan;18(1):334-42 PMID: 9418880
  30. Internal initiation of translation mediated by the 5' leader of a cellular mRNA.
    Nature. 1991 Sep 5;353(6339):90-4 PMID: 1652694
  31. Alternative translation of the proto-oncogene c-myc by an internal ribosome entry site.
    J Biol Chem. 1997 Dec 19;272(51):32061-6 PMID: 9405401
  32. Internal entry of ribosomes is directed by the 5' noncoding region of classical swine fever virus and is dependent on the presence of an RNA pseudoknot upstream of the initiation codon.
    J Virol. 1997 Jan;71(1):451-7 PMID: 8985370
  33. Alternative translation of human fibroblast growth factor 2 mRNA occurs by internal entry of ribosomes.
    Mol Cell Biol. 1995 Jan;15(1):35-44 PMID: 7799942
  34. Mapping of functional domains in eukaryotic protein synthesis initiation factor 4G (eIF4G) with picornaviral proteases. Implications for cap-dependent and cap-independent translational initiation.
    J Biol Chem. 1995 Sep 15;270(37):21975-83 PMID: 7665619
  35. Isolation of human cDNA clones of jun-related genes, jun-B and jun-D.
    Nucleic Acids Res. 1990 May 25;18(10):3047-8 PMID: 2112242
  36. The scanning model for translation: an update.
    J Cell Biol. 1989 Feb;108(2):229-41 PMID: 2645293
  37. The DEAD box protein eIF4A. 1. A minimal kinetic and thermodynamic framework reveals coupled binding of RNA and nucleotide.
    Biochemistry. 1998 Feb 24;37(8):2180-93 PMID: 9485364
  38. The human insulin-like growth factor II leader 1 contains an internal ribosomal entry site.
    Biochim Biophys Acta. 1995 Dec 27;1264(3):403-8 PMID: 8547330
  39. Interaction of polyadenylate-binding protein with the eIF4G homologue PAIP enhances translation.
    Nature. 1998 Apr 2;392(6675):520-3 PMID: 9548260
  40. The DEAD box protein eIF4A. 2. A cycle of nucleotide and RNA-dependent conformational changes.
    Biochemistry. 1998 Feb 24;37(8):2194-206 PMID: 9485365
  41. Bidirectional RNA helicase activity of eucaryotic translation initiation factors 4A and 4F.
    Mol Cell Biol. 1990 Mar;10(3):1134-44 PMID: 2304461
  42. Internal initiation of translation of eukaryotic mRNA directed by a sequence derived from poliovirus RNA.
    Nature. 1988 Jul 28;334(6180):320-5 PMID: 2839775
  43. Amino acid sequence of the human protein synthesis initiation factor eIF-4 gamma.
    J Biol Chem. 1992 Nov 15;267(32):23226-31 PMID: 1429670
  44. Eukaryotic initiation factor 3 is required for poliovirus 2A protease-induced cleavage of the p220 component of eukaryotic initiation factor 4F.
    Proc Natl Acad Sci U S A. 1990 Dec;87(24):9529-33 PMID: 2175904
  45. Novel promoter upstream of the human c-myc gene and regulation of c-myc expression in B-cell lymphomas.
    Mol Cell Biol. 1986 Oct;6(10):3481-9 PMID: 3540591
  46. Regulation of protein synthesis in Tetrahymena: isolation and characterization of polysomes by gel filtration and precipitation at pH 5.3.
    Nucleic Acids Res. 1982 Mar 25;10(6):2145-61 PMID: 7079178
  47. Inhibition of transcription factor activity by poliovirus.
    Cell. 1981 Dec;27(3 Pt 2):555-61 PMID: 6086108
  48. Starting at the beginning, middle, and end: translation initiation in eukaryotes.
    Cell. 1997 Jun 13;89(6):831-8 PMID: 9200601
  49. Regulation of retroviral RNA export.
    Semin Cell Dev Biol. 1997 Feb;8(1):83-90 PMID: 15001110
  50. Cap-binding proteins of eukaryotic messenger RNA: functions in initiation and control of translation.
    Prog Nucleic Acid Res Mol Biol. 1988;35:173-207 PMID: 3065823
  51. Human gene encoding the 78,000-dalton glucose-regulated protein and its pseudogene: structure, conservation, and regulation.
    DNA. 1988 May;7(4):275-86 PMID: 2840249
  52. Nucleotide sequence of cloned cDNA of human c-myc oncogene.
    Nature. 1983 Jun 23-29;303(5919):725-8 PMID: 6304538
  53. eIF4G: translation's mystery factor begins to yield its secrets.
    RNA. 1997 Oct;3(10):1085-104 PMID: 9326485
  54. Internal initiation of translation directed by the 5'-untranslated region of the mRNA for eIF4G, a factor involved in the picornavirus-induced switch from cap-dependent to internal initiation.
    J Biol Chem. 1996 Jan 12;271(2):623-6 PMID: 8557663
  55. 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):5795-9 PMID: 2548189
  56. eIF4G: a multipurpose ribosome adapter?
    Science. 1997 Jan 24;275(5299):500-1 PMID: 9019810
Article Info
Journal
RNA (New York, N.Y.)
Abbr.
RNA
ISSN
1355-8382
DOI
10.1017/s1355838298981080
Published
1998-12-00
Pages
1500-13
Language
English
Region
United States
NLM ID
9509184
PMCID
PMC1369721
Subset
IM
Grants
NIGMS NIH HHS · F32 GM16751 · United States
NIGMS NIH HHS · R01 GM55979 · United States
External Links
PubMed source DOI: 10.1017/s1355838298981080 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2