HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 280, Issue 19, 18610-18622, May 13, 2005

This Article Full Text Full Text (PDF) All Versions of this Article: 280/19/18610    most recent M414014200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Byrd, M. P. Articles by Lloyd, R. E. Search for Related Content PubMed PubMed Citation Articles by Byrd, M. P. Articles by Lloyd, R. E. Social Bookmarking                      What's this?

Translation of Eukaryotic Translation Initiation Factor 4GI (eIF4GI) Proceeds from Multiple mRNAs Containing a Novel Cap-dependent Internal Ribosome Entry Site (IRES) That Is Active during Poliovirus Infection^*

Marshall P. Byrd, Miguel Zamora, and Richard E. Lloyd

From the Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas 77030

Eukaryotic translation initiation factor 4GI (eIF4GI) is an essential scaffolding protein required to recruit the 43 S complex to the 5'-end of mRNA during translation initiation. We have previously demonstrated that eIF4GI protein expression is translationally regulated. This regulation is mediated by cis-acting RNA elements, including an upstream open reading frame and an IRES that directs synthesis of five eIF4GI protein isoforms via alternative AUG initiation codon selection. Here, we further characterize eIF4GI IRES function and show that eIF4GI is expressed from several distinct mRNAs that vary via alternate promoter use and alternate splicing. Several mRNA variants contain the IRES element. We found that IRES activity mapped to multiple regions within the eIF4GI RNA sequence, but not within the 5'-UTR per se. However, the 5'-UTR enhanced IRES activity in vivo and played a role in initiation codon selection. The eIF4GI IRES was active when transfected into cells in an RNA form, and thus, does not require nuclear processing events for its function. However, IRES activity was found to be dependent upon the presence, in cis, of a 5' m⁷guanosine-cap. Despite this requirement, the eIF4GI IRES was activated by 2A protease cleavage of eIF4GI, in vitro, and retained the ability to promote translation during poliovirus-mediated inhibition of cap-dependent translation. These data indicate that intact eIF4GI protein is not required for the de novo synthesis of eIF4GI, suggesting its expression can continue under stress or infection conditions where eIF4GI is cleaved.

Received for publication, December 14, 2004 , and in revised form, March 4, 2005.

^* This research was supported by National Institutes of Health Grants AI 50237 and GM 59803. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Recipient of a NIAID, National Institutes of Health Training Grant T32 AI07471 in molecular virology.

To whom correspondence should be addressed: Dept. of Molecular Virology and Microbiology, Rm. 860E, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030. Tel.: 713-798-8993; Fax: 713-798-5075; E-mail: rlloyd{at}bcm.tmc.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				O. O. Koyuncu and T. Dobner Arginine Methylation of Human Adenovirus Type 5 L4 100-Kilodalton Protein Is Required for Efficient Virus Production J. Virol., May 15, 2009; 83(10): 4778 - 4790. [Abstract] [Full Text] [PDF]

				J. M. Bonderoff, J. L. LaRey, and R. E. Lloyd Cleavage of Poly(A)-Binding Protein by Poliovirus 3C Proteinase Inhibits Viral Internal Ribosome Entry Site-Mediated Translation J. Virol., October 1, 2008; 82(19): 9389 - 9399. [Abstract] [Full Text] [PDF]

				M. Sultan, M. H. Schulz, H. Richard, A. Magen, A. Klingenhoff, M. Scherf, M. Seifert, T. Borodina, A. Soldatov, D. Parkhomchuk, et al. A Global View of Gene Activity and Alternative Splicing by Deep Sequencing of the Human Transcriptome Science, August 15, 2008; 321(5891): 956 - 960. [Abstract] [Full Text] [PDF]

				B. J. Kempf and D. J. Barton Poliovirus 2APro Increases Viral mRNA and Polysome Stability Coordinately in Time with Cleavage of eIF4G J. Virol., June 15, 2008; 82(12): 5847 - 5859. [Abstract] [Full Text] [PDF]

				V. Camerini, D. Decimo, L. Balvay, M. Pistello, M. Bendinelli, J.-L. Darlix, and T. Ohlmann A Dormant Internal Ribosome Entry Site Controls Translation of Feline Immunodeficiency Virus J. Virol., April 1, 2008; 82(7): 3574 - 3583. [Abstract] [Full Text] [PDF]

				B. T. Baranick, N. A. Lemp, J. Nagashima, K. Hiraoka, N. Kasahara, and C. R. Logg Splicing mediates the activity of four putative cellular internal ribosome entry sites PNAS, March 25, 2008; 105(12): 4733 - 4738. [Abstract] [Full Text] [PDF]

				H. Lelouard, E. K. Schmidt, V. Camosseto, G. Clavarino, M. Ceppi, H.-T. Hsu, and P. Pierre Regulation of translation is required for dendritic cell function and survival during activation J. Cell Biol., December 31, 2007; 179(7): 1427 - 1439. [Abstract] [Full Text] [PDF]

				M. R. Reboll, A. Oumard, A. C. Gazdag, I. Renger, B. Ritter, M. Schwarzer, H. Hauser, M. Wood, M. Yamada, K. Resch, et al. NRF IRES activity is mediated by RNA binding protein JKTBP1 and a 14-nt RNA element RNA, August 1, 2007; 13(8): 1328 - 1340. [Abstract] [Full Text] [PDF]

				A. Sharma, J. Masri, O. D. Jo, A. Bernath, J. Martin, A. Funk, and J. Gera Protein Kinase C Regulates Internal Initiation of Translation of the GATA-4 mRNA following Vasopressin-induced Hypertrophy of Cardiac Myocytes J. Biol. Chem., March 30, 2007; 282(13): 9505 - 9516. [Abstract] [Full Text] [PDF]

				N. Oulhen, P. Salaun, B. Cosson, P. Cormier, and J. Morales After fertilization of sea urchin eggs, eIF4G is post-translationally modified and associated with the cap-binding protein eIF4E J. Cell Sci., February 1, 2007; 120(3): 425 - 434. [Abstract] [Full Text] [PDF]

				M. J. Coldwell and S. J. Morley Specific Isoforms of Translation Initiation Factor 4GI Show Differences in Translational Activity Mol. Cell. Biol., November 15, 2006; 26(22): 8448 - 8460. [Abstract] [Full Text] [PDF]

				A. G. Bert, R. Grepin, M. A. Vadas, and G. J. Goodall Assessing IRES activity in the HIF-1{alpha} and other cellular 5' UTRs RNA, June 1, 2006; 12(6): 1074 - 1083. [Abstract] [Full Text] [PDF]

				M.C. DERRY, A. YANAGIYA, Y. MARTINEAU, and N. SONENBERG Regulation of Poly(A)-binding Protein through PABP-interacting Proteins Cold Spring Harb Symp Quant Biol, January 1, 2006; 71(0): 537 - 543. [Abstract] [PDF]

				M. Kozak A second look at cellular mRNA sequences said to function as internal ribosome entry sites Nucleic Acids Res., November 28, 2005; 33(20): 6593 - 6602. [Abstract] [Full Text] [PDF]