Home LiteratureArticle Details
PMID: 11780631 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Poly(A)-binding protein interaction with elF4G stimulates picornavirus IRES-dependent translation.

RNA (New York, N.Y.) ·Vol. 7 ·No. 12 ·2001-12-00 ·Pages 1743-52

Svitkin YV, Imataka H, Khaleghpour K, Kahvejian A, Liebig HD, Sonenberg N

Abstract

The eukaryotic mRNA 3' poly(A) tail and the 5' cap cooperate to synergistically enhance translation. This interaction is mediated, at least in part, by elF4G, which bridges the mRNA termini by simultaneous binding the poly(A)-binding protein (PABP) and the cap-binding protein, elF4E. The poly(A) tail also stimulates translation from the internal ribosome binding sites (IRES) of a number of picornaviruses. elF4G is likely to mediate this translational stimulation through its direct interaction with the IRES. Here, we support this hypothesis by cleaving elF4G to separate the PABP-binding site from the portion that promotes internal initiation. elF4G cleavage abrogates the stimulatory effect of poly(A) tail on translation. In addition, translation in extracts in which elF4G is cleaved is resistant to inhibition by the PABP-binding protein 2 (Paip2). The elF4G cleavage-induced loss of the stimulatory effect of poly(A) on translation was mimicked by the addition of the C-terminal portion of elF4G. Thus, PABP stimulates picornavirus translation through its interaction with elF4G.

MeSH Terms
Encephalomyocarditis virus/genetics Eukaryotic Initiation Factor-4G Peptide Fragments/metabolism Peptide Initiation Factors/metabolism Picornaviridae/genetics Poliovirus/genetics Poly(A)-Binding Proteins Protein Biosynthesis RNA Caps RNA, Messenger/metabolism RNA-Binding Proteins/metabolism Ribosomes/metabolism
Chemicals
Eukaryotic Initiation Factor-4G Peptide Fragments Peptide Initiation Factors Poly(A)-Binding Proteins RNA Caps RNA, Messenger RNA-Binding Proteins
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Svitkin Y V
Department of Biochemistry and McGill Cancer Center, McGill University, Montreal, Quebec, Canada.
Imataka H
Khaleghpour K
Kahvejian A
Liebig H D
Sonenberg N
References (67)
67 references, click to expand
  1. Eukaryotic translation initiation factor 4G is targeted for proteolytic cleavage by caspase 3 during inhibition of translation in apoptotic cells.
    Mol Cell Biol. 1998 Dec;18(12):7565-74 PMID: 9819442
  2. A newly identified N-terminal amino acid sequence of human eIF4G binds poly(A)-binding protein and functions in poly(A)-dependent translation.
    EMBO J. 1998 Dec 15;17(24):7480-9 PMID: 9857202
  3. Cleavage of Poly(A)-binding protein by coxsackievirus 2A protease in vitro and in vivo: another mechanism for host protein synthesis shutoff?
    J Virol. 1999 Jan;73(1):709-17 PMID: 9847377
  4. Cleavage of poly(A)-binding protein by enterovirus proteases concurrent with inhibition of translation in vitro.
    J Virol. 1999 Jan;73(1):718-27 PMID: 9847378
  5. Caspase-3 is necessary and sufficient for cleavage of protein synthesis eukaryotic initiation factor 4G during apoptosis.
    FEBS Lett. 1999 May 28;451(3):332-6 PMID: 10371215
  6. A conserved HEAT domain within eIF4G directs assembly of the translation initiation machinery.
    Mol Cell. 2001 Jan;7(1):193-203 PMID: 11172724
  7. Translational repression by a novel partner of human poly(A) binding protein, Paip2.
    Mol Cell. 2001 Jan;7(1):205-16 PMID: 11172725
  8. Translational control of dosage compensation in Drosophila by Sex-lethal: cooperative silencing via the 5' and 3' UTRs of msl-2 mRNA is independent of the poly(A) tail.
    EMBO J. 1999 Nov 1;18(21):6146-54 PMID: 10545124
  9. Translating ribosomes inhibit poliovirus negative-strand RNA synthesis.
    J Virol. 1999 Dec;73(12):10104-12 PMID: 10559325
  10. Eukaryotic translation initiation factor 4E (eIF4E) binding site and the middle one-third of eIF4GI constitute the core domain for cap-dependent translation, and the C-terminal one-third functions as a modulatory region.
    Mol Cell Biol. 2000 Jan;20(2):468-77 PMID: 10611225
  11. Translation initiation factor modifications and the regulation of protein synthesis in apoptotic cells.
    Cell Death Differ. 2000 Jul;7(7):603-15 PMID: 10889505
  12. Cleavage of polypeptide chain initiation factor eIF4GI during apoptosis in lymphoma cells: characterisation of an internal fragment generated by caspase-3-mediated cleavage.
    Cell Death Differ. 2000 Jul;7(7):628-36 PMID: 10889507
  13. Physical association of eukaryotic initiation factor 4G (eIF4G) with eIF4A strongly enhances binding of eIF4G to the internal ribosomal entry site of encephalomyocarditis virus and is required for internal initiation of translation.
    Mol Cell Biol. 2000 Aug;20(16):6019-29 PMID: 10913184
  14. 3' poly(A) is dispensable for translation.
    Proc Natl Acad Sci U S A. 2000 Aug 1;97(16):9133-7 PMID: 10922069
  15. Multiple portions of poly(A)-binding protein stimulate translation in vivo.
    EMBO J. 2000 Sep 1;19(17):4723-33 PMID: 10970864
  16. Interaction of eIF4G with poly(A)-binding protein stimulates translation and is critical for Xenopus oocyte maturation.
    Curr Biol. 2000 Sep 21;10(18):1147-50 PMID: 10996799
  17. Cap-Poly(A) synergy in mammalian cell-free extracts. Investigation of the requirements for poly(A)-mediated stimulation of translation initiation.
    J Biol Chem. 2000 Oct 13;275(41):32268-76 PMID: 10922367
  18. Interaction of the eIF4G initiation factor with the aphthovirus IRES is essential for internal translation initiation in vivo.
    RNA. 2000 Oct;6(10):1380-92 PMID: 11073214
  19. Picornavirus IRESes and the poly(A) tail jointly promote cap-independent translation in a mammalian cell-free system.
    RNA. 2000 Dec;6(12):1781-90 PMID: 11142378
  20. A prokaryotic-like mode of cytoplasmic eukaryotic ribosome binding to the initiation codon during internal translation initiation of hepatitis C and classical swine fever virus RNAs.
    Genes Dev. 1998 Jan 1;12(1):67-83 PMID: 9420332
  21. Dual function of the messenger RNA cap structure in poly(A)-tail-promoted translation in yeast.
    Nature. 1998 Apr 2;392(6675):516-20 PMID: 9548259
  22. Interaction of polyadenylate-binding protein with the eIF4G homologue PAIP enhances translation.
    Nature. 1998 Apr 2;392(6675):520-3 PMID: 9548260
  23. Recognition of picornavirus internal ribosome entry sites within cells; influence of cellular and viral proteins.
    RNA. 1998 May;4(5):520-9 PMID: 9582094
  24. Protein-primed RNA synthesis by purified poliovirus RNA polymerase.
    Nature. 1998 May 21;393(6682):280-4 PMID: 9607767
  25. Switch from translation to RNA replication in a positive-stranded RNA virus.
    Genes Dev. 1998 Aug 1;12(15):2293-304 PMID: 9694795
  26. Circularization of mRNA by eukaryotic translation initiation factors.
    Mol Cell. 1998 Jul;2(1):135-40 PMID: 9702200
  27. Structure of the DNA repair and replication endonuclease and exonuclease FEN-1: coupling DNA and PCNA binding to FEN-1 activity.
    Cell. 1998 Oct 2;95(1):135-46 PMID: 9778254
  28. 5' cloverleaf in poliovirus RNA is a cis-acting replication element required for negative-strand synthesis.
    EMBO J. 2001 Mar 15;20(6):1439-48 PMID: 11250909
  29. The requirement for eukaryotic initiation factor 4A (elF4A) in translation is in direct proportion to the degree of mRNA 5' secondary structure.
    RNA. 2001 Mar;7(3):382-94 PMID: 11333019
  30. Eukaryotic initiation factor 4G-poly(A) binding protein interaction is required for poly(A) tail-mediated stimulation of picornavirus internal ribosome entry segment-driven translation but not for X-mediated stimulation of hepatitis C virus translation.
    Mol Cell Biol. 2001 Jul;21(13):4097-109 PMID: 11390639
  31. Dual interactions of the translational repressor Paip2 with poly(A) binding protein.
    Mol Cell Biol. 2001 Aug;21(15):5200-13 PMID: 11438674
  32. Poliovirus RNA replication requires genome circularization through a protein-protein bridge.
    Mol Cell. 2001 Mar;7(3):581-91 PMID: 11463383
  33. Studies on the function of polyadenylic acid on poliovirus RNA.
    Cell. 1975 Sep;6(1):41-4 PMID: 170001
  34. Encephalomyocarditis virus RNA. II. Polyadenylic acid requirement for efficient translation.
    J Virol. 1977 Aug;23(2):338-44 PMID: 196111
  35. The protein responsible for the repeating structure of cytoplasmic poly(A)-ribonucleoprotein.
    J Cell Biol. 1983 Mar;96(3):717-21 PMID: 6833379
  36. Differences between translation products of tick-borne encephalitis virus RNA in cell-free systems from Krebs-2 cells and rabbit reticulocytes: involvement of membranes in the processing of nascent precursors of flavivirus structural proteins.
    Virology. 1984 Jun;135(2):536-41 PMID: 6740945
  37. Shutoff of host translation by encephalomyocarditis virus infection does not involve cleavage of the eucaryotic initiation factor 4F polypeptide that accompanies poliovirus infection.
    J Virol. 1985 May;54(2):643-5 PMID: 2985829
  38. A single gene from yeast for both nuclear and cytoplasmic polyadenylate-binding proteins: domain structure and expression.
    Cell. 1986 Jun 20;45(6):827-35 PMID: 3518950
  39. mRNA polyadenylate-binding protein: gene isolation and sequencing and identification of a ribonucleoprotein consensus sequence.
    Mol Cell Biol. 1986 Aug;6(8):2932-43 PMID: 3537727
  40. 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
  41. 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
  42. Role of 3'-end sequences in infectivity of poliovirus transcripts made in vitro.
    J Virol. 1989 Jan;63(1):467-70 PMID: 2535751
  43. The poly(A) binding protein is required for poly(A) shortening and 60S ribosomal subunit-dependent translation initiation.
    Cell. 1989 Sep 8;58(5):857-67 PMID: 2673535
  44. mRNA poly(A) tail, a 3' enhancer of translational initiation.
    Mol Cell Biol. 1990 Jul;10(7):3441-55 PMID: 1972543
  45. The cap and poly(A) tail function synergistically to regulate mRNA translational efficiency.
    Genes Dev. 1991 Nov;5(11):2108-16 PMID: 1682219
  46. Translational enhancement of the poliovirus 5' noncoding region mediated by virus-encoded polypeptide 2A.
    Proc Natl Acad Sci U S A. 1992 Nov 1;89(21):10272-6 PMID: 1332040
  47. 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
  48. Poliovirus RNA synthesis utilizes an RNP complex formed around the 5'-end of viral RNA.
    EMBO J. 1993 Sep;12(9):3587-98 PMID: 8253083
  49. Role for poliovirus protease 2A in cap independent translation.
    EMBO J. 1994 Feb 15;13(4):924-7 PMID: 8112306
  50. 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
  51. Cap-dependent and cap-independent translation by internal initiation of mRNAs in cell extracts prepared from Saccharomyces cerevisiae.
    Mol Cell Biol. 1994 Nov;14(11):7322-30 PMID: 7935446
  52. Insulin-dependent stimulation of protein synthesis by phosphorylation of a regulator of 5'-cap function.
    Nature. 1994 Oct 27;371(6500):762-7 PMID: 7935836
  53. Foot-and-mouth disease virus Lb proteinase can stimulate rhinovirus and enterovirus IRES-driven translation and cleave several proteins of cellular and viral origin.
    J Virol. 1995 Jun;69(6):3465-74 PMID: 7745693
  54. 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
  55. Picornavirus 2A proteinase-mediated stimulation of internal initiation of translation is dependent on enzymatic activity and the cleavage products of cellular proteins.
    Virology. 1995 Nov 10;213(2):549-57 PMID: 7491779
  56. 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
  57. Unique features of internal initiation of hepatitis C virus RNA translation.
    EMBO J. 1995 Dec 1;14(23):6010-20 PMID: 8846793
  58. Canonical eukaryotic initiation factors determine initiation of translation by internal ribosomal entry.
    Mol Cell Biol. 1996 Dec;16(12):6859-69 PMID: 8943341
  59. Functional dissection of eukaryotic initiation factor 4F: the 4A subunit and the central domain of the 4G subunit are sufficient to mediate internal entry of 43S preinitiation complexes.
    Mol Cell Biol. 1996 Dec;16(12):6870-8 PMID: 8943342
  60. 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
  61. General RNA binding proteins render translation cap dependent.
    EMBO J. 1996 Dec 16;15(24):7147-55 PMID: 9003790
  62. 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
  63. Assays for poliovirus polymerase, 3D(Pol), and authentic RNA replication in HeLa S10 extracts.
    Methods Enzymol. 1996;275:35-57 PMID: 9026649
  64. elF4G and its proteolytic cleavage products: effect on initiation of protein synthesis from capped, uncapped, and IRES-containing mRNAs.
    RNA. 1997 Feb;3(2):186-96 PMID: 9042945
  65. Binding of eukaryotic translation initiation factor 4E (eIF4E) to eIF4G represses translation of uncapped mRNA.
    Mol Cell Biol. 1997 Dec;17(12):6876-86 PMID: 9372919
  66. Human eukaryotic translation initiation factor 4G (eIF4G) possesses two separate and independent binding sites for eIF4A.
    Mol Cell Biol. 1997 Dec;17(12):6940-7 PMID: 9372926
  67. A novel functional human eukaryotic translation initiation factor 4G.
    Mol Cell Biol. 1998 Jan;18(1):334-42 PMID: 9418880
Article Info
Journal
RNA (New York, N.Y.)
Abbr.
RNA
ISSN
1355-8382
Published
2001-12-00
Pages
1743-52
Language
English
Region
United States
NLM ID
9509184
PMCID
PMC1370214
Subset
IM
External Links
PubMed source 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: [email protected]

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