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The destabilizing elements in the coding region of c-fos mRNA are recognized as RNA
C L Wellington1, M E Greenberg, J G Belasco
1Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, Massachusetts 02115.
Abstract:
The protein-coding region of the c-fos proto-oncogene transcript contains elements that direct the rapid deadenylation and decay of this mRNA in mammalian cells. The function of these coding region instability determinants requires movement of ribosomes across mRNAs containing them. Three types of mechanisms could account for this translational requirement. Two of these possibilities, (i) that rapid mRNA decay might be mediated by the nascent polypeptide chain and (ii) that it might result from an unusual codon usage, have experimental precedent. Here, we present evidence that the destabilizing elements in the c-fos coding region are not recognized in either of these two ways. Instead, the ability of the c-fos coding region to function as a potent mRNA destabilizer when translated in the +1 reading frame indicates that the signals for rapid deadenylation and decay reside in the sequence or structure of the RNA comprising this c-fos domain.
Insights
The c-fos proto-oncogene mRNA
Area of Science:
- Molecular Biology
- Gene Regulation
- RNA Metabolism
Background:
- The c-fos proto-oncogene plays a crucial role in cellular processes.
- mRNA stability is a key factor in gene expression regulation.
- The coding region of c-fos mRNA contains elements influencing its decay rate.
Purpose of the Study:
- To investigate the mechanisms by which the c-fos coding region directs rapid mRNA deadenylation and decay.
- To determine if nascent polypeptide or codon usage mediates translational requirements for c-fos mRNA instability.
- To identify the specific signals within the c-fos coding region responsible for mRNA destabilization.
Main Methods:
- Experimental analysis of c-fos mRNA decay in mammalian cells.
- Investigating the role of ribosome movement and translation in mRNA instability.
- Testing hypotheses related to nascent polypeptide mediation and unusual codon usage.
- Translating the c-fos coding region in alternative reading frames (+1) to assess destabilizing function.
Main Results:
- The destabilizing elements in the c-fos coding region are not mediated by the nascent polypeptide chain.
- Unusual codon usage does not account for the rapid mRNA decay of c-fos.
- The c-fos coding region functions as a potent mRNA destabilizer when translated in the +1 reading frame.
Conclusions:
- The signals for rapid deadenylation and decay of c-fos mRNA reside within the RNA sequence or structure of the coding domain.
- These instability determinants are recognized during translation, but not through nascent polypeptide or codon usage mechanisms.
- Understanding these mechanisms provides insights into post-transcriptional gene regulation.