The University of Texas Medical School at Houston
gray bar graphic
  UTHSC-H     People Directory     Webmail     Calendar      A-Z
Search
BMB Home | Meet the Faculty | BMB Newsletter | BMB Links | Contact BMB
 
 
About BMB

About BMB

Meet the BMB Faculty Members

Dr. Ambro van Hoof, Assistant Professor

Dr. Ambro van HoofDepartment of Microbiology & Molecular Genetics
Program in Biochemistry and Molecular Biology

University of Texas-Houston Medical School
P.O. Box 20708 - Houston, Texas 77225
(713) 500-5234 Fax: (713) 500-5499
email: Ambro.van.Hoof@uth.tmc.edu

Ph.D, Michigan State University
Postdoctoral Fellow, Howard Hughes Medical Institute &
University of Arizona

mrna degradation & 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.

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.

Figure 1

Selected References


Schaeffer D, Tsanova B, Barbas A, Reis FP, Dastidar EG, Sanchez-Rotunno M, Arraiano CM, van Hoof A. The exosome contains domains with specific endoribonuclease, exoribonuclease and cytoplasmic mRNA decay activities. Nat Struct Mol Biol. 16:56-62, 2009.

Schaeffer D, Meaux S, Clark A, van Hoof A. Determining in vivo activity of the yeast cytoplasmic exosome. Methods Enzymol. 448:227-239, 2008.


Wilson MA, Meaux S, van Hoof A. Diverse aberrancies target yeast mRNAs to cytoplasmic mRNA surveillance pathways. Biochim Biophys Acta. 1779:550-557, 2008.

Shyu AB, Wilkinson MF, van Hoof A. Messenger RNA regulation: to translate or to degrade. EMBO J. 27:471-481, 2008.

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

Wilson MA, Meaux S, van Hoof A. A genomic screen in yeast reveals novel aspects of nonstop mRNA metabolism. Genetics. 177:773-784, 2007.

Meaux S, Van Hoof A. 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, 2006.

van Hoof A Conserved functions of yeast genes support the Duplication, Degeneration and Complementation model for gene duplication. Genetics 171:1455-1461, 2005.

van Hoof, A, Frischmeyer, PA, O'Donnell, K, Dietz,HC, Parker, R. Exosome-mediated recognition and degradation of mRNAs lacking a termination codon. Science 295:2262-2264, 2002.

Search PubMed for a complete list of Dr. van Hoof's publications.