A Fistful of Factors

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Science  09 Jan 2004:
Vol. 303, Issue 5655, pp. 146
DOI: 10.1126/science.303.5655.146b

One of the familiar leitmotifs of biological regulation is a cascade of switches aimed at a crucial go-no go control point. The initiation of protein synthesis is one such point, and assembly of the translational machine, the ribosome, on the messenger RNA (mRNA) is a carefully thought-out decision.

In the developing Drosophila oocyte, oskar mRNA is donated by the surrounding nurse cells, and posterior patterning of the oocyte requires spatially restricted translation of oskar mRNA. Wilhelm et al. show that the protein Cup binds to eukaryotic initiation factor 4E (eIF4E), which sits at the capped 5' end of the mRNA. Cup acts to recruit oskar mRNA to the posterior region and to keep it translationally inactive until it gets there. Nelson et al. show that the Oskar protein appears to exercise a similar regulatory oversight of nanos mRNA, whose translation is inhibited by the interaction between Smaug and Cup, which is in contact with eIF4E bound at the 5' end of the nanos mRNA. Oskar binds to Smaug, and this may result in disruption of the Cup-eIF4E interaction.

Why is it so crucial to control access to eIF4E? Gross et al. describe the structure of the complex between eIF4E and eIF4G. The 4G factor is itself part of a multiprotein complex that serves as a platform for integrating kinase-communicated signals and the subsequent steps of small and large ribosome subunit assembly. The contact between these two factors encompasses a large surface area formed by threading the bracelet-like eIF4G onto the initially unfolded N-terminal α-helix of eIF4E, which then organizes into a fist-like domain, locking eIF4G into place. — GJC

J. Cell Biol. 163, 1197 (2003); EMBO J. 10.1038/sj.emboj.7600026 (2003); Cell 115, 739 (2003)

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