Figure 23'5' interactions: circles of mRNA' a Visualization of circular RNAprotein complexes by atom

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Figure 2  3'5' interactions circles of mRNA.  
a Visualization of circular RNAprotein
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 PABPeIF4GeIF4E
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
PABPPaip1 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 CPEBmaskineIF4E 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.
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• Ruolo di PABP nella traduzione
• In estratti cell free di lievito sinergismo tra
  cap e coda poli(A)
• Interazione tra PABP e eIF4G
• eIF4E, eIF4G, PABP e mRNA forma strutture
  circolari (in vitro)
• Altre proteine che interagiscono con PABP (Paip1,
  2 e eRF3)

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Initiation Factor Activity eIF-1 Fidelity
of AUG codon recognition eIF-1A Facilitate
Met-tRNAiMet binding to small subunit eIF-2
Ternary complex formation eIF-2B (GEF)
GTP/GDP exchange during eIF-2 recycling eIF-3 (10
subunits) Ribosome subunit antiassociation,
binding to 40S subunit eIF-4F (4E, 4A, 4G) mRNA
binding to 40S, ATPase-dependent RNA helicase
activity eIF-4A ATPase-dependent RNA
helicase eIF-4E 5' cap recognition
eIF-4G Scaffold for of eIF-4E and -4A in the
eIF-4F complex eIF-4B Stimulates helicase,
binds simultaneously with eIF-4F eIF-4H           
   Similar to eIF4B    eIF-5 Release of
eIF-2 and eIF-3, ribosome-dependent GTPase eIF5B
Subunit joining eIF-6 Ribosome subunit
antiassociation
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Inizio di traduzione nellmRNA di poliovirus
AUG
AUG
AUG
p
U
p
A
U
G
AUG
IRES Internal ribosome entry site
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Saggio dellmRNA bicistronico
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eIF3
40S
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CARATTERISTICHE DI UN "SISTEMA VIVENTE"
replicazione evoluzione
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FUNZIONI DELL'RNA NELLA CELLULA MODERNA
traduzione rRNA, mRNA, tRNA maturazione
rRNA snoRNA, RNasi MRP splicing snRNA,
introni gruppi I e II maturazione tRNA RNasi
P sintesi DNA primers, telomerasi
traslocaz. proteine srpRNA
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PERCHE' L'RNA?

• l'RNA deve essere venuto prima del DNA
• l'RNA deve essere venuto prima delle
• proteine
• molti coenzimi hanno un
• ribonucleotide nella struttura
• l'RNA può agire come catalizzatore