Overproduction of a conserved domain of fission yeast and mammalian translation initiation factor eIF4G causes aberrant cell morphology and results in disruption of the localization of F-actin and the organization of microtubules.
BACKGROUND
The recruitment of mRNA for translation involves the assembly at the 5'cap of a complex of three initiation factors: the cap binding protein eIF4E, the ATP-dependent RNA helicase eIF4A and the scaffold protein eIF4G. eIF4G mediates the binding of this mRNA-protein complex to the 43S ribosomal preinitiation complex. There is growing recognition that the components of the translational apparatus interact functionally with cytoskeletal components. Here we report specific effects of the over-expression of human and fission yeast eIF4G domains on cell morphology in Schizosaccharomyces pombe.


RESULTS
A single gene encoding fission yeast eIF4G was identified and demonstrated to be essential. We have over-expressed fragments corresponding to the conserved functional domains of eIF4G. At expression levels that did not disrupt rates of overall translation or protein accumulation, a fragment of S. pombe eIF4G, 4G-NOB, corresponding to the minimal region of human eIF4G required to support cap-independent mRNA recruitment, was found to impair cell proliferation in fission yeast. This resulted from defects in cytokinesis, and was associated with the disruption of both microtubules and actin microfilaments. The over-expressed fragment was itself localized to the cell ends, the nuclear periphery and the septum.


CONCLUSIONS
This is the first demonstration of a link between a translation initiation factor and mechanisms controlling cell morphology. The data suggest a direct or indirect interaction between the functional domains of eIF4G and cellular structures involved in cytokinesis.
Hashemzadeh-Bonehi
Lida
L
Biochemistry Laboratory, School of Biological Sciences, University of Sussex, Brighton BN1 9QG, UK.
Curtis
Penelope S
PS
Morley
Simon J
SJ
Thorpe
Julian R
JR
Pain
Virginia M
VM
D000199:Actins / Q000378:metabolism*; D000595:Amino Acid Sequence; D001665:Binding Sites; D002470:Cell Survival; D039603:Eukaryotic Initiation Factor-4G / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D005656:Fungal Proteins / Q000737:chemistry / Q000378:metabolism*; D049452:Green Fluorescent Proteins; D006801:Humans; D008164:Luminescent Proteins / Q000378:metabolism; D008870:Microtubules / Q000378:metabolism*; D008969:Molecular Sequence Data; D014176:Protein Biosynthesis; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012568:Schizosaccharomyces / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D017386:Sequence Homology, Amino Acid
D000199:Actins; D039603:Eukaryotic Initiation Factor-4G; D005656:Fungal Proteins; D008164:Luminescent Proteins; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins