mRNAs containing extensive secondary structure in their 5' non-coding region translate efficiently in cells overexpressing initiation factor eIF-4E.
Cellular eukaryotic mRNAs (except organellar) contain at the 5' terminus the structure m7(5')Gppp(5')N (where N is any nucleotide), termed cap. Cap recognition by eukaryotic initiation factor eIF-4F plays an important role in regulating the overall rate of translation. eIF-4F is believed to mediate the melting of mRNA 5' end secondary structure and facilitate 43S ribosome binding to capped mRNAs. eIF-4E, the cap-binding subunit of eIF-4F, plays an important role in cell growth; its overexpression results in malignant transformation of rodent cells, and its phosphorylation is implicated in signal transduction pathways of mitogens and growth factors. The molecular mechanism by which eIF-4E transforms cells is not known. Here, we report that overexpression of eIF-4E facilitates the translation of mRNAs containing excessive secondary structure in their 5' non-coding region. This effect may represent one mechanism by which eIF-4E regulates cell growth and transforms cells in culture.
Koromilas
A E
AE
Department of Biochemistry, Faculty of Medicine, McGill University, Montreal, Canada.
Lazaris-Karatzas
A
A
Sonenberg
N
N
D016475:3T3 Cells; D000818:Animals; D001483:Base Sequence; D015139:Blotting, Southern; D004247:DNA / Q000302:isolation & purification / Q000378:metabolism*; D039561:Eukaryotic Initiation Factor-4E; D015870:Gene Expression; D051379:Mice; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D010448:Peptide Initiation Factors / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D010957:Plasmids; D014176:Protein Biosynthesis; D012315:RNA Caps / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D015183:Restriction Mapping; D012694:Serine; D014162:Transfection
D039561:Eukaryotic Initiation Factor-4E; D009838:Oligodeoxyribonucleotides; D010448:Peptide Initiation Factors; D012315:RNA Caps; D012333:RNA, Messenger; D012694:Serine; D004247:DNA