[Translational control by the poly(A) binding protein: a check for mRNA integrity].
The eukaryotic mRNA 3' poly(A) tail and the 5' cap cooperate to synergistically enhance translation. This interaction is mediated by a ribonucleoprotein network that contains, at a minimum, the poly(A) binding protein (PABP), the capbinding protein eIF4E and a scaffolding protein, eIF4G. eIF4G, in turn, contains binding sites for eIF4A and eIF3, a 40S ribosome-associated initiation factor. The combined cooperative interactions within this "closed loop" mRNP among other effects enhance the affinity of eIF4E for the 5' cap by lowering its dissociation rate and, ultimately, facilitate the formation of 48S and 80S ribosome initiation complexes. The PABP-poly(A) interaction also stimulates initiation driven by picomavirus' internal ribosomal entry sites (IRESs), a process that requires eIF4G but not eIF4E. PABP, therefore, should be considered a canonical initiation factor, integral to initiation complex formation. Poly(A)-mediated translation is subjected to regulation by the PABP-interacting proteins Paip1 and Paip2. Paip1 acts as a translational enhancer. In contrast, Paip2 strongly inhibits translation by promoting dissociation of PABP from poly(A) and by competing with eIF4G for binding to PABP.
Svitkin
Yuri V
YV
Sonenberg
Nahum
N
D000818:Animals; D039561:Eukaryotic Initiation Factor-4E / Q000378:metabolism; D039603:Eukaryotic Initiation Factor-4G; D039642:Eukaryotic Initiation Factors / Q000378:metabolism; D006801:Humans; D011061:Poly A / Q000378:metabolism; D039102:Poly(A)-Binding Proteins / Q000502:physiology*; D011485:Protein Binding; D014176:Protein Biosynthesis / Q000502:physiology*; D012315:RNA Caps / Q000502:physiology*; D020871:RNA Stability / Q000502:physiology*; D012333:RNA, Messenger / Q000502:physiology*; D016601:RNA-Binding Proteins / Q000502:physiology
D039561:Eukaryotic Initiation Factor-4E; D039603:Eukaryotic Initiation Factor-4G; D039642:Eukaryotic Initiation Factors; D039102:Poly(A)-Binding Proteins; D012315:RNA Caps; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D011061:Poly A