Display Settings:


Send to:

Choose Destination
See comment in PubMed Commons below
RNA. 2001 Nov;7(11):1578-88.

Cellular mutants define a common mRNA degradation pathway targeting cytokine AU-rich elements.

Author information

  • 1Institute of Medical Microbiology, University of Basel, Switzerland.


To functionally classify AU-rich elements (AREs) from six different cytokine mRNAs, we made use of two previously described HT1080-derived cellular mutants (slowA, slowC) that lack a function required for the rapid degradation of interleukin-3 (IL-3) mRNA. Here we show that the defect is specific for ARE-containing mRNAs, whereas nonsense-mediated decay is intact. Degradation of beta-globin reporter transcripts mediated by the AREs of IL-3, GM-CSF, and TNFalpha, as well as by the structurally different and less potent AREs of IL-2 and IL-6, is impaired in both mutants. All these reporter transcripts are also sensitive to decay induced by ectopic expression of the RNA-binding protein tristetraprolin in the slowC background. Thus, we concluded that the mutants slowA and slowC define a common mRNA degradation pathway that targets cytokine AREs. In NIH3T3 cells, this decay pathway becomes incapacitated by upstream signaling from p38 MAP- or PI3-kinases, which independently stabilize cytokine ARE-containing transcripts. In contrast, c-fos ARE-directed mRNA degradation proceeds through a different pathway not affected by these kinases.

[PubMed - indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Write to the Help Desk