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Molecular and Cellular Biology, January 2008, p. 40-49, Vol. 28, No. 1
0270-7306/08/$08.00+0     doi:10.1128/MCB.01298-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Identification of Internal Ribosome Entry Segment (IRES)-trans-Acting Factors for the Myc Family of IRESs{triangledown} ,{ddagger}

Laura C. Cobbold,1,{dagger} Keith A. Spriggs,1,{dagger} Stephen J. Haines,1 Helen C. Dobbyn,1 Christopher Hayes,2 Cornelia H. de Moor,1 Kathryn S. Lilley,3 Martin Bushell,1 and Anne E. Willis1*

Centre for Biomolecular Sciences, University of Nottingham, University Park, Nottingham NG7 2RD, United Kingdom,1 School of Chemistry, University of Nottingham, University Park, Nottingham NG7 2RD, United Kingdom,2 Cambridge Systems Biology Centre, University of Cambridge, Tennis Court Rd., Cambridge CB2 1GA, United Kingdom3

Received 19 July 2007/ Returned for modification 14 August 2007/ Accepted 12 October 2007

The proto-oncogenes c-, L-, and N-myc can all be translated by the alternative method of internal ribosome entry whereby the ribosome is recruited to a complex structural element (an internal ribosome entry segment [IRES]). Ribosome recruitment is dependent upon the presence of IRES-trans-acting factors (ITAFs) that act as RNA chaperones and allow the mRNA to attain the correct conformation for the interaction of the 40S subunit. One of the major challenges for researchers in this area is to determine whether there are groups of ITAFs that regulate the IRES-mediated translation of subsets of mRNAs. We have identified four proteins, termed GRSF-1 (G-rich RNA sequence binding factor 1), YB-1 (Y-box binding protein 1), PSF (polypyrimidine tract binding protein-associated splicing factor), and its binding partner, p54nrb, that bind to the myc family of IRESs. We show that these proteins positively regulate the translation of the Myc family of oncoproteins (c-, L-, and N-Myc) in vivo and in vitro. Interestingly, synthesis from the unrelated IRESs, BAG-1 and Apaf-1, was not affected by YB-1, GRSF-1, or PSF levels in vivo, suggesting that these three ITAFs are specific to the myc IRESs. Myc proteins play a role in cell proliferation; therefore, these results have important implications regarding the control of tumorigenesis.

* Corresponding author. Mailing address: School of Pharmacy, Pharmacy Building, University of Nottingham, University Park, Nottingham NG7 2RD, United Kingdom. Phone: 44 115 8467095. Fax: 44 115 8468877. E-mail: anne.willis{at}nottingham.ac.uk

{triangledown} Published ahead of print on 29 October 2007.

{ddagger} Supplemental material for this article may be found at http://mcb.asm.org/.

{dagger} L.C.C. and K.A.S. contributed jointly to the project.

Molecular and Cellular Biology, January 2008, p. 40-49, Vol. 28, No. 1
0270-7306/08/$08.00+0     doi:10.1128/MCB.01298-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



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