Identification of internal ribosome entry segment (IRES)-trans-acting factors for the Myc family of IRESs

Cobbold, L. C., Spriggs, K. A., Haines, S. J., Dobbyn, H. C., Hayes, C., de Moor, C. H., Lilley, K. S., Bushell, M. and Willis, A. E. (2008) Identification of internal ribosome entry segment (IRES)-trans-acting factors for the Myc family of IRESs. Molecular and Cellular Biology, 28(1), pp. 40-49. (doi: 10.1128/MCB.01298-07) (PMID:17967896) (PMCID:PMC2223313)

Abstract

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.

• Item Type: Articles
• Additional Information: This work was supported by grants from the BBSRC (L.C.C., K.A.S., H.C.D., S.J.H., and M.B.).
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Bushell, Professor Martin
• Authors: Cobbold, L. C., Spriggs, K. A., Haines, S. J., Dobbyn, H. C., Hayes, C., de Moor, C. H., Lilley, K. S., Bushell, M., and Willis, A. E.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Molecular and Cellular Biology
• Publisher: American Society for Microbiology
• ISSN: 0270-7306
• ISSN (Online): 1098-5549
• Published Online: 29 October 2007