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.

1 Follower
12 Reads
  • Source
    • "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). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Differential regulation of transcript stability is an effective means by which an organism can modulate gene expression. A well characterised example is glutamine signalled degradation of specific transcripts in Aspergillus nidulans. In the case of areA, which encodes a wide-domain transcription factor mediating nitrogen metabolite repression, the signal is mediated through a highly conserved region of the 3' UTR. Utilising this RNA sequence we isolated RrmA, an RNA recognition motif protein. Disruption of the respective gene led to loss of both glutamine signalled transcript degradation as well as nitrate signalled stabilization of niaD mRNA. However, nitrogen starvation was shown to act independently of RrmA in stabilizing certain transcripts. RrmA was also implicated in the regulation of arginine catabolism gene expression and the oxidative stress responses at the level of mRNA stability. ΔrrmA mutants are hypersensitive to oxidative stress. This phenotype correlates with destabilization of eifE and dhsA mRNA. eifE encodes eIF5A, a translation factor within which a conserved lysine is post-translationally modified to hypusine, a process requiring DhsA. Intriguingly, for specific transcripts RrmA mediates both stabilization and destabilization and the specificity of the signals transduced is transcript dependent, suggesting it acts in consort with other factors which differ between transcripts.
    Molecular Microbiology 07/2013; 89(5). DOI:10.1111/mmi.12324 · 4.42 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Colorectal cancers (CRC) are one of the most common causes of morbidity and mortality in high-income countries. Targeted screening programs have resulted in early treatment and a substantial decrease in mortality. However, treatment strategies for CRC still require improvement. Understanding the etiology and pathogenesis of CRC would provide tools for improving treatment of patients with this disease. It is only recently that deregulation of the protein synthesis apparatus has begun to gain attention as a major player in cancer development and progression. Among the numerous steps of protein synthesis, deregulation of the process of translation initiation appears to play a key role in cancer growth and proliferation. This manuscript discusses a fascinating and rapidly growing field exploring translation initiation as a fundamental component in CRC development and progression and summarizing CRC treatment perspectives based on agents targeting translation initiation.
    CANCER AND METASTASIS REVIEW 03/2012; 31(1-2):387-95. DOI:10.1007/s10555-012-9349-9 · 7.23 Impact Factor
  • [Show abstract] [Hide abstract]
    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.
    Amino Acids 09/2012; 44(2). DOI:10.1007/s00726-012-1387-7 · 3.29 Impact Factor
Show more


12 Reads
Available from