Translational control: recognition of the methylated 5' end and an internal sequence in eukaryotic mRNA by the initiation factor that binds methionyl-tRNAfMet.
Structural analogs of the methylated 5' end (cap) of eukaryotic mRNA, such as 7-methylguanosine 5'-monophosphate, specifically inhibit both GTP-dependent binding of Met-tRNAfMet and binding of globin mRNA to eukaryotic initiation factor 2 (eIF-2). Addition of purified eIF-2 effectively relieves the cap analog-induced inhibition of globin mRNA translation. The analog competitively inhibits the function of eIF-2 and of mRNA in protein synthesis. Binding to eIF-2 of capped mRNA as well as noncapped mRNA, such as Mengo virus RNA, can be inhibited completely by free cap molecules, but much more cap is needed to inhibit binding of Mengo virus RNA. mRNA, whether or not it is capped, competitively inhibits the binding of Met-tRNAfMet to eIF-2. These results provide compelling evidence that eIF-2 recognizes mRNA. It is shown that binding of mRNA to eIF-2 is primarily at an internal sequence, and secondarily through the cap. A model for the function of eIF-2 is presented that can account for all these properties. This model can provide a molecular basis for the differential translation of mRNA species, whether or not they are capped.
D005057:Eukaryotic Cells; D005914:Globins / Q000096:biosynthesis; D006160:Guanosine Triphosphate / Q000378:metabolism; D008715:Methionine; D008745:Methylation; D008954:Models, Biological; D010448:Peptide Initiation Factors; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000378:metabolism*; D012343:RNA, Transfer / Q000378:metabolism*; D012367:RNA, Viral / Q000378:metabolism; D012270:Ribosomes / Q000378:metabolism
D010448:Peptide Initiation Factors; D012333:RNA, Messenger; D012367:RNA, Viral; D006160:Guanosine Triphosphate; D005914:Globins; D012343:RNA, Transfer; D008715:Methionine
FEBS Lett. 1976 Dec 31;72(2):309-13
16386047
J Biol Chem. 1976 Sep 25;251(18):5657-62
965382
Proc Natl Acad Sci U S A. 1978 Jan;75(1):209-13
272636
Eur J Biochem. 1976 AUG 1;67(1):247-56
823012
Cell. 1976 Dec;9(4 PT 2):645-53
1017010
Science. 1968 Jun 28;160(3835):1452-4
4297545
Nat New Biol. 1973 Mar 14;242(115):35-8
4512006
J Mol Biol. 1973 May 25;76(3):379-403
4732074
FEBS Lett. 1976 May 1;64(2):326-31
179883
J Virol. 1974 Sep;14(3):598-610
4368674
Cell. 1974 Nov;3(3):197-9
4373171
J Mol Biol. 1976 Jul 5;104(3):637-58
950671
Cell. 1975 Oct;6(2):185-95
1182800
Nature. 1975 May 1;255(5503):33-7
165427
Proc Natl Acad Sci U S A. 1975 Mar;72(3):1189-93
165487
Proc Natl Acad Sci U S A. 1974 Aug;71(8):3199-203
4607060
Proc Natl Acad Sci U S A. 1973 Apr;70(4):1222-6
4197930
Proc Natl Acad Sci U S A. 1972 Nov;69(11):3317-21
4508325
Nature. 1976 Jul 1;262(5563):32-7
180425
Proc Natl Acad Sci U S A. 1975 Apr;72(4):1258-62
165500
Proc Natl Acad Sci U S A. 1976 Feb;73(2):375-80
174106
Proc Natl Acad Sci U S A. 1976 Feb;73(2):327-30
174102
Nature. 1974 Oct 4;251(5474):385-8
4421673
J Mol Biol. 1973 Apr 15;75(3):575-8
4737561
Proc Natl Acad Sci U S A. 1976 Jan;73(1):19-23
1061116
Nature. 1976 Mar 25;260(5549):359-60
1256580
Nature. 1976 May 27;261(5558):291-4
944862