mRNA degradation and quality control of gene expression in eukaryotes

Gene expression is a complex process that all life forms need to carry out in a precisely controlled fashion. The degradation of mRNA serves important roles in this process. For example degradation rates of individual mRNAs can be regulated and affect mRNA abundance, and thus how much of each protein is produced by translation. mRNA decay also plays an important role in maintaining the overall fidelity of gene expression by preferentially degrading aberrant mRNAs that are made by mistakes during mRNA processing reactions. One example of aberrant mRNAs that are extremely rapidly degraded are those that lack a stop codon. Such "nonstop" mRNAs are produced frequently by premature addition of a poly(A) tail. Click here for a model of how nonstop mRNAs are recognized and degraded.

The yeast Saccharomyces cerevisiae and probably most other eukaryotes have two general pathways to degrade mRNA. These two pathways both degrade stable and unstable mRNAs. Thus, the key to understanding differential mRNA degradation is to understand the interactions of a particular mRNA with the basal machinery.

One of the two pathways of mRNA degradation is carried out by the exosome. The exosome is a complex containing multiple 3' to 5' exonucleases that not only degrades mRNA, but also functions in the maturation of many RNAs from 3' extended precursors. This raises interesting questions such as why there are so many RNases in one complex, and how does the exosome completely degrade some RNAs, but process others.

Research in my lab is focused on understanding in molecular detail how a particular mRNA interacts with the mRNA decay machinery and how this causes its degradation. The rapid recognition and degradation of nonstop mRNAs serve as a useful model in these experiments.

SELECTED PUBLICATIONS:

Wilson MA, Meaux S, and van Hoof A (2008) Diverse aberrancies target yeast mRNAs to cytoplasmic mRNA surveillance pathways. BBA-GRM in press [abstract]/[full text pdf]

Shyu A-B, Wilkinson MF and van Hoof A (2008) Messenger RNA regulation: to translate or to degrade. EMBO J. 27:471-481 [abstract]/[full text pdf]

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 [abstract]/[full text pdf]

Wilson MA, 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 MA, 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]

van Hoof A, Parker R (1999) The exosome: a proteasome for RNA? Cell 99:347

Search PubMed for more papers by Ambro van Hoof