Dual function of the messenger RNA cap structure in poly(A)-tail-promoted translation in yeast

Abstract

The messenger RNA 3′ poly(A) tail critically affects the initiation and control of translation in eukaryotes1,2,3. By analogy to elements involved in transcription initiation, the poly(A) tail has been described as a ‘translational enhancer’ that enhances the ‘translational promoter’ activity of the mRNA 5′-cap structure3,4. Elongation or shortening of the poly(A) tail regulates translation during development2. Here we show, using cell-free and in vivo translation analyses in Saccharomyces cerevisiae, that the poly(A) tail can act as an independent ‘translational promoter’, delivering ribosomes to uncapped mRNAs even if their 5′ end is blocked. When mRNAs compete for ribosome binding, neither the cap structure nor the poly(A) tail alone is enough to drive efficient translation, but together they synergize and direct ribosome entry to the 5′ end. The cap structure both promotes ribosome recruitment, together with the poly(A) tail, and tethers recruited ribosomes to the 5′ end. Correct choice of translation initiation codons and the function of translational regulators acting on the 5′ untranslated region are thus ensured by the functional interaction of the poly(A) tail with the cap structure.

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Figure 1: Poly(A)-tail-promoted translation is insensitive to a physically blocked mRNA 5′ end.
Figure 2: Initiation codon choice in cap- and poly(A)-tail-promoted translation.
Figure 3: In vivo analysis of CAT-reporter mRNAs.
Figure 4: mRNA competition determines cooperativity between cap structure and poly(A) tail and enforces 5′-end-dependent ribosome recruitment.

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Acknowledgements

We thank A. Sachs and P. Sarnow for reagents and stimulating discussions, and A.Ephrussi, A. Jenny, F. Stewart, and the members of the Hentze lab for comments on the manuscript. This work was supported by an EMBO fellowship to T.P.

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Correspondence to Matthias W. Hentze.

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Preiss, T., Hentze, M. Dual function of the messenger RNA cap structure in poly(A)-tail-promoted translation in yeast. Nature 392, 516–520 (1998). https://doi.org/10.1038/33192

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