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
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)
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
Inizio di traduzione nell’mRNA di poliovirus
pUp
AUG
AUG
AUG
AUG
UUUCCUUUU
AUG
IRES= Internal ribosome entry site
Saggio dell’mRNA bicistronico
cap
luciferasi
CAT
+/-
+++
cap
CAT
IRES
+++
+++
cap
CAT
IRES
cap
CAT
(+/0)
luciferasi
+++
(+)
4F
luciferasi
IRES
luciferasi
+++
eIF3
40S
CARATTERISTICHE DI UN "SISTEMA VIVENTE"
replicazione
evoluzione
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
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