High impact information on 7-METHYL-GUANOSINE-5'-TRIPHOSPHATE

• Rapamycin or amino acid withdrawal increases, whereas insulin strongly inhibits, the recovery of 4EBP1 and raptor on 7-methyl-GTP Sepharose [1].
• Pak2 binds to and phosphorylates initiation factor (eIF)4G, which inhibits association of eIF4E with m(7)GTP, reducing initiation [2].
• Known cap-binding proteins, such as eIF4E and the nuclear cap-binding complex, are not detectable in the enzyme preparation, and PARN itself binds to m(7)GTP-Sepharose and is eluted specifically with the cap analog m(7)GTP [3].
• Eukaryotic translation initiation factor 4E (eIF4E) is an essential component of the translational machinery that binds m(7)GTP and mediates the recruitment of capped mRNAs by the small ribosomal subunit [4].
• Two initiation inhibitors, aurintricarboxylic acid and 7-methylguanosine 5'-triphosphate, were found to affect polysome size and the fraction of mRNA in polysomes in an opposite manner [5].

Biological context of 7-METHYL-GUANOSINE-5'-TRIPHOSPHATE

• Translation of 3c, unlike that of 3a and 3b, was insensitive to the presence of the 5' cap analog 7-methyl-GTP, and it was unaffected by alteration of the sequence contexts for initiation on the 3a and 3b ORFs [6].
• There was no evidence for further methylation of m(7)GTP when it was used as a substrate for the methyltransferase [7].
• A similar mode of interaction with 7-methyl-GTP was found for human cap binding protein eIF4E [8].

Anatomical context of 7-METHYL-GUANOSINE-5'-TRIPHOSPHATE

• The cap analogues 7-methylguanosine 5'-phosphate [m7G(5')p], 7-methylguanosine 5'-triphosphate [m7G(5')ppp] and 2'-O-methylguanosine 5'-triphosphate [Gm(5')ppp] inhibit the translation of capped globin mRNA and encephalomyocarditis (EMC) RNA (a naturally uncapped mRNA) in a reticulocyte cell-free system [9].

Associations of 7-METHYL-GUANOSINE-5'-TRIPHOSPHATE with other chemical compounds

• Phenyl azide substituted and benzophenone-substituted phosphonamides of 7-methylguanosine 5'-triphosphate as photoaffinity probes for protein synthesis initiation factor eIF-4E and a proteolytic fragment containing the cap-binding site [10].

Gene context of 7-METHYL-GUANOSINE-5'-TRIPHOSPHATE

• The association constant values of recombinant eIF4E for 20 different cap analogues cover six orders of magnitude; with the highest affinity observed for m(7)GTP (approximately 1.1 x 10(8) M(-1)) [11].
• Alternatively cell lysates were exposed to 7-methyl GTP Sepharose beads in order to isolate the cap-binding protein eIF-4E [12].
• This was confirmed further by 7-methyl-GTP Sepharose isolation of eIF-4E with which 4E-BP1 coprecipitates [12].
• The cap analogue m(7)GTP, but not GTP, inhibited VPg-eIF(iso)4E complex formation, suggesting that VPg and cellular mRNAs compete for eIF(iso)4E binding [13].
• Eukaryotic translation initiation factor 4E (eIF4E) binds to the m(7)GTP of capped mRNAs and is an essential component of the translational machinery that recruits the 40S small ribosomal subunit [14].

Analytical, diagnostic and therapeutic context of 7-METHYL-GUANOSINE-5'-TRIPHOSPHATE

• High-pressure liquid chromatography analysis confirmed the production of m(7)GTP by the GTP methyltransferase activity of H68A [15].
• Fluorescence titration experiments with eIF4E and the nuclear cap-binding complex CBC indicated affinities for RTP and RpppG that were two to four orders of magnitude lower than those of m(7)GTP and m(7)GpppG [16].

References