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Removal of poly(A) and consequent degradation of c-fos mRNA facilitated by 3′ AU-rich sequences

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Abstract

The c-fos proto-oncogene provides a good system to study the processes underlying messenger RNA degradation. After growth factor stimulation of susceptible cells, the c-fos transcription rate transiently increases from a low basal level by as much as 50-fold1, producing a large amount of exceedingly unstable c-fos mRNA that is rapidly degraded1–3. Here, we investigate the c-fos mRNA degradation process, and find that: (1) ongoing translation of the c-fos mRNA itself is required for its degradation; (2) after synthesis, the mRNA poly(A) tail is rapidly removed, in a translation-dependent manner, leading to accumulation of apparently de-adenylated RNA; (3) deletion or replacement of an AU-rich sequence at the mRNA 3′ end significantly stabilizes the mRNA; (4) deletion of the 3′ AU-rich sequences dramatically slows the poly(A) shortening rate. These results suggest that the 3′ AU-rich sequences act to destabilize the mRNA by directing rapid removal of the mRNA poly(A) tract.

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Author notes

  1. Richard Treisman: To whom correspondence should be addressed: Imperial Cancer Research Fund, PO Box 123, Lincoln's Inn Fields, London WC2A3PX, UK.

Authors and Affiliations

  1. MRC Laboratory of Molecular Biology, MRC Centre, Hills Road, Cambridge, CB2 2QH, UK

    Tim Wilson & Richard Treisman

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  1. Tim Wilson
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  2. Richard Treisman
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Wilson, T., Treisman, R. Removal of poly(A) and consequent degradation of c-fos mRNA facilitated by 3′ AU-rich sequences. Nature 336, 396–399 (1988). https://doi.org/10.1038/336396a0

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