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Molecular and Cellular Biology, November 2008, p. 6658-6667, Vol. 28, No. 21
0270-7306/08/$08.00+0 doi:10.1128/MCB.00738-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Mélanie C. Derry,1,
Xiaoshan Wang,1
Akiko Yanagiya,1
Juan José Berlanga,2
Ann-Bin Shyu,3
Hiroaki Imataka,4
Kalle Gehring,1 and
Nahum Sonenberg1,5*
Department of Biochemistry,1 McGill Cancer Centre, McGill University, 3655 Promenade Sir William Osler, Montreal, Québec, Canada H3G 1Y6,5 Centro de Biologìa Molecular Severo Ochoa, Facultad de Ciencias, Universidad Autõnoma de Madrid, Cantoblanco 28049 Madrid, Spain,2 Department of Biochemistry and Molecular Biology, University of Texas Medical School, Houston, Texas 77030,3 RIKEN Systems and Structural Biology Center, Tsurumi-ku, Yokohama, Japan4
Received 7 May 2008/ Returned for modification 18 June 2008/ Accepted 13 August 2008
Poly(A)-binding protein (PABP) stimulates translation initiation by binding simultaneously to the mRNA poly(A) tail and eukaryotic translation initiation factor 4G (eIF4G). PABP activity is regulated by PABP-interacting (Paip) proteins. Paip1 binds PABP and stimulates translation by an unknown mechanism. Here, we describe the interaction between Paip1 and eIF3, which is direct, RNA independent, and mediated via the eIF3g (p44) subunit. Stimulation of translation by Paip1 in vivo was decreased upon deletion of the N-terminal sequence containing the eIF3-binding domain and upon silencing of PABP or several eIF3 subunits. We also show the formation of ternary complexes composed of Paip1-PABP-eIF4G and Paip1-eIF3-eIF4G. Taken together, these data demonstrate that the eIF3-Paip1 interaction promotes translation. We propose that eIF3-Paip1 stabilizes the interaction between PABP and eIF4G, which brings about the circularization of the mRNA.
Published ahead of print on 25 August 2008.
Y.M. and M.C.D. contributed equally to the work.
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