Removal of poly(A) and consequent degradation of c-fos mRNA facilitated by 3' AU-rich sequences.
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-fold, producing a large amount of exceedingly unstable c-fos mRNA that is rapidly degraded. 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 deadenylated 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.
Wilson
T
T
MRC Laboratory of Molecular Biology, MRC Centre, Cambridge, UK.
Treisman
R
R
D001483:Base Sequence; D008969:Molecular Sequence Data; D011061:Poly A / Q000378:metabolism*; D014176:Protein Biosynthesis; D011519:Proto-Oncogenes; D015347:RNA Probes; D012333:RNA, Messenger / Q000378:metabolism*
D015347:RNA Probes; D012333:RNA, Messenger; D011061:Poly A