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Gene expression is a complex process that all organisms must carry out in a precisely controlled fashion and is in part controlled by the differential degradation of mRNA. One of the major question that remains to be answered is how some mRNAs are targeted for rapid degradation, while other mRNAs are relatively stable.

We are trying to understand the interaction between the mRNA decay machinery and its substrates, using mRNAs that lack a stop codon as a model system. Such "nonstop" mRNAs are extremely rapidly degraded in both human and yeast cells. The degradation of nonstop mRNAs is likely a quality control function, whereby mRNAs that arose by premature polyadenylation or other mistakes are rapidly degraded. We use the yeast Saccharomyces cerevisiae to study nonstop mRNA decay, because it allows a combination of genetic and biochemical approaches to the problem. We expect that the specific recognition of nonstop mRNAs will also reveal general principles governing the decay of normal mRNAs.

Selected Publications:

S. Meaux, A. van Hoof, and K. Baker (2008) Nonsense-mediated mRNA decay in yeast does not require PAB1 or a poly(A) tail. Mol. Cell 29:134-140 [full text pdf]

Wilson M, Meaux S, van Hoof A (2007) A genomic screen in yeast reveals novel aspects of nonstop mRNA metabolism. Genetics 177:773-784. [abstract]/[full text pdf]

Meaux S, van Hoof A (2006) Yeast transcripts cleaved by an internal ribozyme provide new insight into the role of the cap and poly(A) tail in translation and mRNA decay. RNA 12:1323-1337. [abstract]/[full text pdf]

Wilson M, Meaux S, Parker R, van Hoof A (2005) Genetic interactions between [PSI+] and nonstop mRNA decay affect phenotypic variation. Proc. Natl. Acad. Sci. U.S.A. 102:10244-10249. [abstract]/[full text pdf]

van Hoof A (2005) Conserved functions of yeast genes support the Duplication, Degeneration and Complementation model for gene duplication. Genetics 171:1455-1461. [abstract]/[full text pdf]/[suplementary material pdf]

van Hoof A, Frischmeyer PA, Dietz HC, Parker R (2002) Exosome-mediated recognition and degradation of mRNAs lacking a termination codon. Science 295:2262 [abstract]/[full text]

Frischmeyer PA, van Hoof A, O'Donnell K, Guerrerio AL, Parker R, Dietz HC (2002) An mRNA surveillance mechanism that eliminates transcripts lacking termination codons. Science 295:2258 [abstract]/[full text]