Proof of principle experiments have shown that -1 programmed ribosomal frame shift signals can act as mRNA suicide elements capable of directing messages to the nonsense mediated mRNA decay pathway. Preliminary data has shown that eukaryotic mRNA on which frame shifted ribosomes encounter premature stop codons are subsequently targeted for rapid degradation. Thus, PRF signals may be utilized as a means to post-transcriptionally regulate gene expression by altering the half-life of cellular mRNAs. The proposed research project utilizes bioinformatics methodologies to identify programmed -1 ribosomal frame shift signals from several eukaryotic model organisms. A bioinformatics protocol for the identification PRF signals is in development. Results will be correlated with a series of DNA microarray experiments designed to detect PRF signal containing mRNA transcripts in Saccharomyces cerevisiae. This will provide validation for the bioinformatics results and a resource for refinement of the PRF signal model. A searchable online database will be created for the scientific community to utilize. The proposed studies will serve as the foundation for further research into a newly discovered paradigm of gene regulation.
| Belew, Ashton T; Hepler, Nicholas L; Jacobs, Jonathan L et al. (2008) PRFdb: a database of computationally predicted eukaryotic programmed -1 ribosomal frameshift signals. BMC Genomics 9:339 |
| Jacobs, Jonathan L; Belew, Ashton T; Rakauskaite, Rasa et al. (2007) Identification of functional, endogenous programmed -1 ribosomal frameshift signals in the genome of Saccharomyces cerevisiae. Nucleic Acids Res 35:165-74 |
| Jacobs, Jonathan L; Dinman, Jonathan D (2004) Systematic analysis of bicistronic reporter assay data. Nucleic Acids Res 32:e160 |
