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Paola Londei - Translational regulation: from the archaea to the eukarya of assays so far performed, including interaction with the β and γ subunits to form the intact trimer and capacity of binding met-tRNAi. To investigate in vivo phosphorylation, we have performed immunoprecipitation assays with anti α-subunit antibodies on whole cell lysates, followed by western blotting with anti-phosphoserine antibodies. Preliminary results indicate that the a/eIF2 α-subunit is indeed phosphorylated in vivo, and that the amount of phosphorylation increases following heat-shock, indicating that the modification may inhibit protein synthesis. Work is in progress to confirm and expand these results and to elucidate the underlying molecular mechanism. A still mysterious protein: IF6 The factor known as aIF6 (archaea) and eIF6 (eukarya) is a monomeric protein of about 25 kDa. Eukaryotic IF6 was originally described as a ribosome anti-association factor, which interacted with the large ribosomal subunits inhibiting the formation of active 80S ribosomes. Later experiments revealed that depletion of eIF6 in yeast depressed the biosynthesis of 60S ribosomal subunits, but had otherwise no specific effect on translation initiation, assigning to the factor a main role in ribosome synthesis. Further experiments in mammals, however, have confirmed a role for eIF6 in translational regulation, that may or may not co-exist with other functions. 60S ribosomal subunit must release eIF6 to enter the translation cycle; eIF6 dissociation from the ribosome is triggered by the phosphorylation of the factor carried out by certain regulatory kinases. More 12 recently, it has been shown that heterozygous knockout mice for eIF6 have defective translational initiation. Finally, it has been <strong>report</strong>ed that eIF6 depletion inhibits miRNA-induced gene silencing in both human cells and in nematodes. Despite the many functions <strong>report</strong>ed, the mechanism of action of eIF6 in any of them remains unknown. Archaeal IF6 shares a high degree of homology with eIF6, both in primary sequence and in three-dimensional structure. Our recent work has revealed that S. solfataricus aIF6 has a ribosome anti-associating activity and is a potent inhibitor of protein synthesis in vitro. We have mapped for the first time the ribosomal binding site of aIF6: it lies in the centre of the 30S-contacting face of the large ribosomal subunit. Our model of the aIF6/50S complex reveals that the factor inhibits the formation of the 70S ribosome by masking a number of RNA and protein determinants that bridge the two subunits. These data confirm the identity of IF6 as a translation factor and rationalize its anti-associating activity in molecular detail. Work is in progress to unravel the mechanism whereby aIF6 dissociates from the 50S subunit. Preliminary data indicate that this may entail a novel type of protein modification, possibly in association with a ribosome-dependent GTPase activity, yet to be identified. Selected publications Benelli D, Marzi S, Mancone C, Alonzi T, La Teana A, Londei P. Function and ribosomal localization of aIF6, a translational regulator shared by archaea and eukarya. Nucleic Acids Res. 2008, Epub.
AREA2 Pathogenetic mechanisms of microbially associated diseases
Page 1 and 2: Istituto Pasteur Fondazione Cenci B
Page 3 and 4: Contents Forward by Paolo Amati, P
Page 5 and 6: Research area 6: New antimicrobial
Page 7 and 8: REPORT OF ACTIVITY 2007-2008 Boards
Page 9 and 10: REPORT OF ACTIVITY 2007-2008 Dario
Page 11 and 12: REPORT OF ACTIVITY 2007-2008 Meetin
Page 13: AREA1 Molecular biology of microorg
Page 16 and 17: P. Amati - Role of the early phases
Page 18 and 19: A. Boffi - Escherichia coli strains
Page 20 and 21: D. De Biase - The glutamate-based a
Page 22 and 23: A. Faggioni - Control of latency an
Page 27 and 28: A structural biology study of schis
Page 29 and 30: P a r t i c i p a n t s : Luigi Lem
Page 31 and 32: P a r t i c i p a n t s : Gianni Pr
Page 33 and 34: P a r t i c i p a n t s : Lucia Nen
Page 35 and 36: P a r t i c i p a n t s : Alessandr
Page 37 and 38: P a r t i c i p a n t s : Maurizio
Page 39: AREA3 Molecular genetics of eukaryo
Page 42 and 43: F. Ascenzioni - Development and ana
Page 44 and 45: P. Ballario - Molecular machines an
Page 46 and 47: I. Bozzoni - RNA-RNA and RNA-protei
Page 48 and 49: P. Caiafa - Crosstalk between poly(
Page 50 and 51: G. Camilloni - DNA topoisomerases a
Page 52 and 53: P. Costantino - The role of the DAG
Page 54 and 55: M. d’Erme - Epigenetic modificati
Page 56 and 57: P. Dimitri - Drosophila melanogaste
Page 58 and 59: L. Fabiani - DNA replication mechan
Page 60 and 61: C. Falcone - New tools in decipheri
Page 62 and 63: L. Frontali - New complex mitochond
Page 64 and 65: M. Gatti - The role of membrane tra
Page 66 and 67: A. Giacomello - Biology and physiol
Page 68 and 69: A. Gulino - Regulation of the Hedge
Page 70 and 71: M. Levrero - Histone Acetyltransfer
Page 72 and 73: F. Mangia - Molecular regulation of
Page 74 and 75:
A. Musarò - Study of the molecular
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R. Negri - Role of the presumptive
Page 78 and 79:
S. Pimpinelli - Heterochromatin, ge
Page 80 and 81:
M. Stefanini - Biological character
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M. Tripodi - Molecular mechanisms o
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C. Turano - Roles of ERp57 in DNA r
Page 86 and 87:
G. Zardo - Identification of novel
Page 89 and 90:
P a r t i c i p a n t s : Carlo Tra
Page 91 and 92:
P a r t i c i p a n t s : Giulia De
Page 93 and 94:
P a r t i c i p a n t s : Giovanna
Page 95 and 96:
P a r t i c i p a n t s : Francesco
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P a r t i c i p a n t s : Bruno Bot
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P a r t i c i p a n t s : Sergio Fu
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P a r t i c i p a n t s : Maria Egl
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P a r t i c i p a n t s : Stefano C
Page 105:
AREA5 Cellular and molecular immuno
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V. Barnaba - Innovative strategies
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R. Foà - Potential role of miRNAS
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E. Piccolella - Analysis of the mol
Page 114 and 115:
A. Santoni - Molecular mechanism un
Page 116 and 117:
I. Screpanti - Analysis of the role
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R. Sorrentino - The role of HLA-B27
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L. Tuosto - CD28 co-stimulatory mol
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E. Ziparo - The role of Toll Like R
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Peptide effectors of innate immunit
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P a r t i c i p a n t s : Gustavo P
Page 129 and 130:
P a r t i c i p a n t s : Roberta C
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P a r t i c i p a n t s : Giovanna
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P a r t i c i p a n t s : Livia Di
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P a r t i c i p a n t s : Marino Ar
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AREA7 Biology of malaria and other
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Della Torre - Petrarca - Bionomical
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A. Tramontano - Computational Analy
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Year 2007 Barile L, Chimenti I, Gae
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Puglisi R, Bevilacqua A, Carlomagno
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BIBLIOGRAPHY Conigliaro A, Colletti
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BIBLIOGRAPHY Muscolini M, Cianfrocc
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