Cell Biology & Molecular Genetics

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Author: search.filters.author.Jacobs, Jonathan LEnd date: 2009

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    PRFdb: A database of computationally predicted eukaryotic programmed -1 ribosomal frameshift signals
    (Springer Nature, 2008-07-17) Belew, Ashton T; Hepler, Nicholas L; Jacobs, Jonathan L; Dinman, Jonathan D
    The Programmed Ribosomal Frameshift Database (PRFdb) provides an interface to help researchers identify potential programmed -1 ribosomal frameshift (-1 PRF) signals in eukaryotic genes or sequences of interest. To identify putative -1 PRF signals, sequences are first imported from whole genomes or datasets, e.g. the yeast genome project and mammalian gene collection. They are then filtered through multiple algorithms to identify potential -1 PRF signals as defined by a heptameric slippery site followed by an mRNA pseudoknot. The significance of each candidate -1 PRF signal is evaluated by comparing the predicted thermodynamic stability (ΔG°) of the native mRNA sequence against a distribution of ΔG° values of a pool of randomized sequences derived from the original. The data have been compiled in a user-friendly, easily searchable relational database. The PRFdB enables members of the research community to determine whether genes that they are investigating contain potential -1 PRF signals, and can be used as a metasource of information for cross referencing with other databases. It is available on the web at http://dinmanlab.umd.edu/prfdb .
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    mRNA Suicide: Destabilization by Programmed Ribosomal Frameshifting
    (2006-04-17) Jacobs, Jonathan L; Dinman, Jonathan D; Cell Biology & Molecular Genetics; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)
    Cis-acting mRNA elements that promote programmed -1 ribosomal frameshifting (-1 PRF) redirect a fraction of translating ribosomes into a new translational reading frame. In viruses, these signals typically direct the translation of alternative protein products from a single mRNA. However, programmed frameshifts could also direct elongating ribosomes to premature termination codons, in which case the mRNAs could become targets for degradation by the nonsense mediated mRNA decay pathway (NMD). Computational analyses revealed the presence of 10,340 consensus -1 PRF signals in the <i>Saccharomyces cerevisiae</i> genome. Of the 6,353 yeast open reading frames (ORFs) included in this study, 1,275 are predicted to have at least one strong and statistically significant -1 PRF signal. In contrast to viral frameshifting, the predicted outcomes of nearly all of these genomic frameshift signals would direct ribosomes to premature termination codons, in theory making these mRNAs substrates for NMD. Nine of these predicted -1 PRF signals were tested empirically, eight of which promoted efficient levels of PRF in vivo. This study also demonstrates that viral -1 PRF signals are sufficient to target a reporter mRNA for degradation via NMD. Furthermore, several of -1 PRF signals from the yeast genome were also shown to act as NMD-dependent mRNA destabilizing element. Importantly, these signals are found in genes whose mRNAs are known to be natural targets for NMD. These findings support the hypothesis that PRF may be used by cellular mRNAs to initiate "mRNA suicide". A model is presented in which programmed frameshifting acts as a general post-transcriptional regulatory mechanism to control gene expression by regulating mRNA abundance.