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Multiple elements in the c-fos protein-coding region facilitate mRNA deadenylation and decay by a mechanism coupled
S C Schiavi1, C L Wellington, A B Shyu
1Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, Massachusetts 02115.
Abstract:
The c-fos proto-oncogene transcript is one of the most labile mammalian mRNAs known. Rapid degradation of c-fos mRNA is mediated by both the c-fos protein-coding region and an AU-rich element in the 3'-untranslated region. Here we present evidence that the c-fos coding region contains multiple destabilizing elements that can function independently to facilitate both deadenylation and decay of mRNA. The ability of these coding region destabilizing elements to direct deadenylation and decay requires the assembly of ribosomes at the 5' end of this domain and, most likely, translation of the message.
Insights
The c-fos proto-oncogene (a key cellular regulator) mRNA is rapidly degraded. Destabilizing elements within its coding region, activated by ribosome activity and translation, accelerate this decay process.
Area of Science:
- Molecular Biology
- Gene Regulation
- mRNA Stability
Background:
- The c-fos proto-oncogene transcript is known for its rapid degradation in mammalian cells.
- Both the protein-coding region and the 3'-untranslated region (UTR) containing an AU-rich element contribute to c-fos mRNA instability.
Purpose of the Study:
- To investigate the role of the c-fos coding region in mRNA destabilization.
- To identify specific destabilizing elements within the c-fos coding sequence.
- To understand the mechanisms, including translation, that regulate c-fos mRNA decay.
Main Methods:
- Analysis of c-fos mRNA degradation pathways.
- Identification of destabilizing elements within the c-fos coding region.
- Investigation of the role of ribosome assembly and translation in mRNA decay.
Main Results:
- The c-fos coding region contains multiple independent destabilizing elements.
- These elements facilitate both deadenylation and decay of c-fos mRNA.
- The function of these coding region elements is dependent on ribosome binding and likely mRNA translation.
Conclusions:
- The c-fos coding region actively participates in regulating mRNA stability.
- Translation and ribosome activity are crucial for the destabilizing function of elements within the c-fos coding region.
- Understanding these mechanisms provides insights into the rapid turnover of c-fos mRNA and its role in cellular processes.