Disease relevance of EIF1AX

• Here, we assess the use of IF1/eIF1A and IF2/eIF5B in universal and partial phylogenetic studies by comparison of sequence information from species within all three phylogenetic domains and among closely related strains of Haemophilus parainfluenzae [1].
• Overexpression of the human eIF-1A cDNA in Escherichia coli and subsequent purification enabled us to prepare large quantities of active factor [2].

High impact information on EIF1AX

• The 40S subunit in 48S complexes formed at the initiation codon of mRNA is bound to eukaryotic initiation factor (eIF) 3, eIF1, eIF1A, and an eIF2/GTP/Met-tRNAi(Met) ternary complex and can therefore not join a 60S subunit directly to form an 80S ribosome [3].
• The assembly defects of the OB-fold mutation can be attributed to reduced 40S-binding of eIF1A, whereas deltaC impairs eIF1A function on the ribosome [4].
• Truncating the C-terminus (deltaC) or mutating OB-fold residues (66-70) of eIF1A reduced general translation in vivo but increased GCN4 translation (Gcd- phenotype) in a manner suppressed by overexpressing TC [4].
• Unexpectedly, Imp13 also shows export activity towards the translation initiation factor eIF1A and is thus a case where a single importin beta-like receptor transports different substrates in opposite directions [5].
• We demonstrate herein that (i) the "analogous" translation initiation factors IF-1 and eIF-1A are actually related in sequence, (ii) the "eukaryotic" translation factor SUI1 is universal in distribution, and (iii) the eukaryotic/archaeal translation factor eIF-5A is homologous to the bacterial translation factor EF-P [6].

Biological context of EIF1AX

• The protein amino acid sequence of wheat germ eIF-4C is 68% identical with the mammalian protein, and, allowing for the most conservative substitutions, the proteins are 76% similar [7].
• IF1/eIF1A and IF2/eIF5B, two conserved translation initiation factors are involved in this important step of protein biosynthesis [1].
• Disruption of either isoleucine residue in the eIF1A C-terminal sequence DIDDI reduces the rate constant for GTP hydrolysis by approximately 20-fold, whereas changing the aspartic acid residues has no effect [8].
• To better elucidate its precise role in promoting the translation initiation process, the yeast form of eIF1A has been identified in Saccharomyces cerevisiae and purified to homogeneity on the basis of its cross-reaction with antibodies prepared against mammalian eIF1A [9].
• Deletion/disruption of TIF11 demonstrates that eIF1A is essential for cell growth [9].

Anatomical context of EIF1AX

• In contrast, yeast eIF1A and eIF5B have been reported to interact in the absence of ribosomes [10].
• The amino acid sequence of many peptides from rabbit reticulocyte and wheat germ eIF-4C have been determined chemically [7].
• The moderate abundance means that eIF-1A is equal to or in excess of native 40 S subunits and suggests that the factor may not be limiting for protein synthesis, a conclusion reinforced by the failure of overproduced eIF-1A to stimulate translation rates in transiently transfected COS-1 cells [2].
• The level of eIF-1A in HeLa cells determined by Western immunoblotting is 0.01% of total protein, which corresponds to 0.2 molecules of eIF-1A/ribosome [2].
• Results show that IGF-I intraovarian injection increased blastocyst yields and mRNA expression of Glut-1 and eIF1A to levels found in embryos produced from adult cows [11].

Associations of EIF1AX with chemical compounds

• From the chemical sequencing of the rabbit protein, it was noted that at least two different eIF-4C molecules were present which differed by conservative substitutions at three positions (2 aspartic acid for glutamic acid switches and 1 valine for isoleucine switch) [7].

Other interactions of EIF1AX

• Here, we have identified the binding interface between human eIF1A and the C-terminal domain of eIF5B by using solution NMR [10].
• Here, we report the quantitative characterization of energetic interactions between eIF1A, eIF5 and the AUG codon in an in vitro reconstituted yeast translation initiation system [12].
• In addition, eIF1A, eIF4F (or the C-terminal fragment of eIF4G), and eIF4A strongly stimulated the assembly of this complex, whereas eIF4B had no effect [13].

Analytical, diagnostic and therapeutic context of EIF1AX

• NMR titration experiments showed that eIF1A binds single-stranded RNA oligonucleotides in a site-specific, but non-sequence-specific manner, hinting at an mRNA interaction rather than specific rRNA or tRNA binding [14].
• The RA for eIF1A was higher (P </= 0.05) in 8- to 16-cell embryos derived from cows than those from the control group [11].

References