Protein Synthesis and Degradation
Molecular mechanism of poliovirus Sabin vaccine strain attenuation
Recruitment of poliovirus (PV) RNA to the human ribosome requires the coordinated interaction of the viral internal ribosome entry site (IRES) and several host cellular initiation factors and IRES trans-acting factors (ITAFs). Attenuated PV Sabin strains contain point mutations in the PV IRES domain V (dV) that inhibit viral translation. Remarkably, attenuation is most apparent in cells of the central nervous system, but the molecular basis to explain this is poorly understood. The dV contains binding sites for eukaryotic initiation factor 4G (eIF4G) and polypyrimidine tract–binding protein (PTB).eIF4F: A Retrospective
The original purification of the heterotrimeric eIF4F was published over 30 years ago (Grifo, J. A., Tahara, S. M., Morgan, M. A., Shatkin, A. J., and Merrick, W. C. (1983) J. Biol. Chem. 258, 5804–5810). Since that time, numerous studies have been performed with the three proteins specifically required for the translation initiation of natural mRNAs, eIF4A, eIF4B, and eIF4F. These have involved enzymatic and structural studies of the proteins and a number of site-directed mutagenesis studies. The regulation of translation exhibited through the mammalian target of rapamycin (mTOR) pathway is predominately seen as the phosphorylation of 4E-BP, an inhibitor of protein synthesis that functions by binding to the cap binding subunit of eIF4F (eIF4E).Evidence That Base-pairing Interaction between Intron and mRNA Leader Sequences Inhibits Initiation of HAC1 mRNA Translation in Yeast
Background: Hac1 protein, encoded by a cytoplasmically spliced mRNA, activates the unfolded protein response to maintain cellular protein homeostasis and alleviate endoplasmic reticulum stress.Results: Under non-stress conditions, translation initiation on the HAC1 mRNA is repressed.Conclusion: Base-pairing interaction between the 5′ leader and intron represses translation initiation on the HAC1 mRNA.Significance: A unique mechanism of intron-mediated inhibition of ribosomal scanning.
