Presentazione sul tema: "Figure 2 | 3'–5' interactions: circles of mRNA"— Transcript della presentazione:
1Figure 2 | 3'–5' interactions: circles of mRNA Figure 2 | 3'–5' interactions: circles of mRNA. a | Visualization of circular RNA–protein complexes by atomic-force microscopy. Complexes formed on capped, polyadenylated double-stranded RNA in the presence of eIF4G, poly(A)-binding protein (PABP) and eIF4E91. (Picture provided by A. Sachs and reprinted with permission.) b | Model of messenger-RNA circularization and translational activation by PABP–eIF4G–eIF4E interactions. eIF4G simultaneously binds to eIF4E and PABP7, 9, 14, 53, 55, thereby circularizing the mRNA91 and mediating the synergistic stimulatory effect on translation of the cap and poly(A) tail by enhancing the formation of the 48S complex53, 54, 92. c | Model of mRNA circularization and translational activation by PABP–Paip1 interactions. Paip1 is a PABP-interacting protein that binds eIF4A93, acting as a translational co-activator. d | Model of mRNA circularization and translational repression by CPEB–maskin–eIF4E interactions. RNA-associated CPEB binds maskin, which in turn binds to the eIF4E. This configuration of factors precludes the binding of eIF4G to eIF4E and thus inhibits assembly of the 48S complex13. e | Model of translational repression by heterogeneous nuclear ribonucleoproteins (hnRNPs). The differentiation control element (DICE), located in the 3' UTR of 15-lipoxygenase mRNA, inhibits translation initiation by preventing the joining of the 60S ribosomal subunit to the 43S complex located at the AUG codon. This inhibition is mediated by hnRNP proteins K and E1. The inhibitory event probably targets one of the initiation factors involved in the GTP hydrolysis that releases the initiation factors and the joining of the 60S ribosomal subunit2, 94. ORF, open reading frame.
7Ruolo di PABP nella traduzione In estratti “cell free” di lievito sinergismo tra cap e coda poli(A)Interazione tra PABP e eIF4GeIF4E, eIF4G, PABP e mRNA forma strutture circolari (in vitro)Altre proteine che interagiscono con PABP (Paip1, 2 e eRF3)
9Initiation Factor Activity eIF Fidelity of AUG codon recognitioneIF-1A Facilitate Met-tRNAiMet binding to small subuniteIF Ternary complex formationeIF-2B (GEF) GTP/GDP exchange during eIF-2 recyclingeIF-3 (10 subunits) Ribosome subunit antiassociation, binding to 40S subuniteIF-4F (4E, 4A, 4G) mRNA binding to 40S, ATPase-dependent RNA helicase activityeIF-4A ATPase-dependent RNA helicaseeIF-4E 5' cap recognitioneIF-4G Scaffold for of eIF-4E and -4A in the eIF-4F complexeIF-4B Stimulates helicase, binds simultaneously with eIF-4FeIF-4H Similar to eIF4B eIF Release of eIF-2 and eIF-3, ribosome-dependent GTPaseeIF5B Subunit joiningeIF Ribosome subunit antiassociation
10Inizio di traduzione nell’mRNA di poliovirus AUGAUGAUGAUGUUUCCUUUUAUGIRES= Internal ribosome entry site
14Model for assembly of 48S complexes on EMCV-like IRESs Model for assembly of 48S complexes on EMCV-like IRESs. Structural domains of the IRES and regions of contact with the following factors as determined by footprinting are shown: eIF4G/4A complex (blue/green), ITAF 45 (diamonds), PTB (gray). PTB contains four RRM domains and binds multiple sites on EMCV-like IRESs; such binding (indicated by a dotted line) therefore may stabilize a specific conformation of the IRES. The recruitment of a 40S ribosomal subunit (red) carrying initiator tRNA and eIF3 (yellow) is shown. See text for details.