Jonathan Dinman's Lab Home Page
TIBS Cover ArticleJBC cover designed by Dr. Dinman
 
 

 

 


Jan. 2014

CCR5 mRNA Unfolding Pathways.
in BioPhy Journal

Nov. 2013

Eukaryotic rpL10 drives ribosomal rotation
in NAR

Aug. 2013

PEMV kissing loop-TSS enhances Translational Reinitiation
in JVI

Mar. 2013

Yeast telomere Length, -1 PRF and NMD
in Translation

Jan 2013

Altering SARS -1PRF efficiency affects RNA production
in Viruses (journal)

Dec 2012

RNA dimerization plays a role in SARS -1 PRF
in NAR


 

 

Welcome!

My laboratory studies three distinct yet overlapping fields of study: virology, ribosome structure/function relationships, and regulation of gene expression.

 

 

Ribosome Structure & Function

One important function of the ribosome is to faithfully maintain translational reading frame. Viral mRNA signals that abrogate this function by programming ribosomes to shift frame have proved to be of tremendous utility in elucidating the molecular mechanisms underlying this essential task. The newly available atomic resolution structures of ribosomes mark a critical milestone in the quest to link ribosome structure with function, and our studies on PRF have begun to link ribosome structure with translational frame maintenance. We have shown that both the biophysical interactions between ribosomal proteins rRNAs and tRNAs, and the biochemical properties of ribosome-associated enzymatic activities are both important for proper reading frame maintenance. On a broader scale, our work also is consistent with the hypothesis that communication between the different functional centers of the ribosome is critical for coordinating ribosome structure with its various functions. Of particular interest, recent structural analyses of mutants that we had previously identified as affecting frameshifting reveals that they correspond to critical points of contact between specific ribosomal components. This positions us for to conduct reverse genetic studies linking ribosome structure with function.


Regulation of Gene Expression

Since "biological systems tend to use whatever works", there is no reason to believe that programmed ribosomal frameshifting is exclusively utilized by viruses. Based on this philosophy, we are pursuing a bioinformatic program designed to identify functional programmed -1 ribosomal frameshift signals in the genomic databases. This effort employs a combination of computational, DNA microarray, and traditional "wet lab" approaches. We have found that programmed ribosomal frameshift signals can act as mRNA suicide elements, suggesting that PRF is used to post-transcriptionally regulate the abundance of specific mRNAs and their encoded protein products. The reverse side of this coin is the question of how viruses have evolved to circumvent this regulatory mechanism, allowing them to utilize programmed ribosomal frameshifting without having their mRNAs degraded.


Virology

The maintenance of correct translational reading frame is fundamental to the integrity of the protein synthetic process, and ultimately to cell growth and viability. Despite this, it has been demonstrated that certain viruses utilize specific signals on their mRNAs that induce elongating ribosomes to shift reading frame. The highly controlled efficiencies of PRF events ensure that the proper stoichiometric ratio of viral structural to enzymatic proteins are available for viral particle assembly. Changing frameshifting efficiencies alters this ratio, preventing proper viral particle assembly and interfering with virus propagation. Thus, programmed ribosomal frameshifting presents a promising new target for anti-viral pharmacological intervention. We are characterizing a series of yeast mutants and drugs in order to identify new targets for antiviral therapies. We are also working to create a reverse genetic system for a dsRNA virus of yeast.


The PRFdb

The Saccharomyces cerevisiae Programmed Ribosomal Frameshifting Database is now publicly available.
http://dinmanlab.umd.edu/prfdb/ or http://prfdb.umd.edu
Our plasmids in genbank format


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