The role of eIF5A in protein synthesis

Cell cycle (Georgetown, Tex.) (Impact Factor: 4.57). 11/2011; 10(21):3617-8. DOI: 10.4161/cc.10.21.17850
Source: PubMed


Comment on: Henderson A, et al. Proc Natl Acad Sci USA 2011; 108:6415-9.

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    • "There is strong evidence that both eIF5A expression and its post-translational modification are altered in ΔrrmA strains, with both the eifE and dhsA transcripts being significantly less stable in the ΔrrmA background. eIF5A is a highly conserved translation factor involved in initiation and/or elongation (Saini et al., 2009; Henderson and Hershey, 2011). It has also been implicated as having a role in eukaryotic stress responses (Ohn and Anderson, 2010; Wang et al., 2012) and nonsense mediated decay (Kang and Hershey, 1994; Schrader et al., 2006) and as a key determinant of cell proliferation making it a key factor in pathogenicity of various diseases including cancer (Kaiser, 2012). "
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    ABSTRACT: The protein eukaryotic initiation factor 5A (eIF5A) is highly conserved among archaea and eukaryotes, but not in bacteria. Bacteria have the elongation factor P (EF-P), which is structurally and functionally related to eIF5A. eIF5A is essential for cell viability and the only protein known to contain the amino acid residue hypusine, formed by post-translational modification of a specific lysine residue. Although eIF5A was initially identified as a translation initiation factor, recent studies strongly support a function for eIF5A in the elongation step of translation. However, the mode of action of eIF5A is still unknown. Here, we analyzed the oligomeric state of yeast eIF5A. First, by using size-exclusion chromatography, we showed that this protein exists as a dimer in vitro, independent of the hypusine residue or electrostatic interactions. Protein-protein interaction assays demonstrated that eIF5A can form oligomers in vitro and in vivo, in an RNA-dependent manner, but independent of the hypusine residue or the ribosome. Finally, small-angle X-ray scattering (SAXS) experiments confirmed that eIF5A behaves as a stable dimer in solution. Moreover, the molecular envelope determined from the SAXS data shows that the eIF5A dimer is L-shaped and superimposable on the tRNA(Phe) tertiary structure, analogously to the EF-P monomer.
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