Identification of internal ribosome entry segment (IRES)-trans-acting factors for the Myc family of IRESs.
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.
Cobbold
Laura C
LC
School of Pharmacy, Pharmacy Building, University of Nottingham, University Park, Nottingham NG7 2RD, United Kingdom.
Spriggs
Keith A
KA
Haines
Stephen J
SJ
Dobbyn
Helen C
HC
Hayes
Christopher
C
de Moor
Cornelia H
CH
Lilley
Kathryn S
KS
Bushell
Martin
M
Willis
Anne E
AE
D000818:Animals; D002460:Cell Line; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D034521:Nuclear Matrix-Associated Proteins / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D000072670:PTB-Associated Splicing Factor; D011132:Polyribosomes / Q000378:metabolism; D011485:Protein Binding; D014176:Protein Biosynthesis / Q000235:genetics; D016271:Proto-Oncogene Proteins c-myc / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D012270:Ribosomes / Q000378:metabolism*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*
D034521:Nuclear Matrix-Associated Proteins; D009687:Nuclear Proteins; D000072670:PTB-Associated Splicing Factor; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D015534:Trans-Activators