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Interaction of polyadenylate-binding protein with the eIF4G homologue PAIP enhances translation

Nature volume 392, pages 520–523 (1998)Cite this article

Abstract

In the initiation of translation in eukaryotes, binding of the small ribosomal subunit to the messenger RNA results from recognition of the 5′ cap structure (m7GpppX) of the mRNA by the cap-binding complex eIF4F1. eIF4F is itself a three-subunit complex comprising the cap-binding protein eIF4E2, eIF4A, an ATP-dependent RNA helicase3, and eIF4G, which interacts with both eIF4A and eIF4E and enhances cap binding by eIF4E4. The mRNA 3′ polyadenylate tail and the associated poly(A)-binding protein (PABP) also regulate translational initiation5, probably by interacting with the 5′ end of the mRNA6,7. In yeast8,9 and plants10, PABP interacts with eIF4G8,9 but no such interaction has been reported in mammalian cells. Here, we describe a new human PABP-interacting protein, PAIP-1, whose sequence is similar to the central portion of eIF4G and which interacts with eIF4A. Overexpression of PAIP-1 in COS-7 cells stimulates translation, perhaps by providing a physical link between the mRNA termini.

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Figure 1: Identification of PAIP-1 and its homology with eIF4G.
Figure 2: Interaction of PAIP-1 with PABP.
Figure 3: PAIP-1 overexpression enhances translation.
Figure 4: Proposed models for the bridging of 5′ and 3′ mRNA ends in eukaryotes.

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Acknowledgements

We thank G. Dreyfuss and H. Traschel for monoclonal antibodies against human PABP and eIF4A, respectively; J. Bag for human PABP cDNA; M. Park for the cDNA library; Y. Svitkin for HeLa extracts; O. Donzé for luciferase plasmid; and G. Cosentino, A.-C. Gingras, B. Raught and K.Khaleghpour for comments on the manuscript. This work was supported by a grant from the MRC of Canada to N.S. A.W.B.C. was supported by a joint training award from National Health Research and Development-MRC of Canada. N.S. is a distinguished scientist of the MRC of Canada and a Howard Hughes international scholar.

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  1. Department of Biochemistry and McGill Cancer Centre, McGill University, Montreal, H3G 1Y6, Quebec, Canada

    Andrew W. B. Craig, Ashkan Haghighat, Annie T. K. Yu & Nahum Sonenberg

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  1. Andrew W. B. Craig
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Correspondence to Nahum Sonenberg.

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Craig, A., Haghighat, A., Yu, A. et al. Interaction of polyadenylate-binding protein with the eIF4G homologue PAIP enhances translation. Nature 392, 520–523 (1998). https://doi.org/10.1038/33198

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