| Maurille J. Fournier
Professor Emeritus of Biochemistry and Molecular Biology, University of Massachusetts
Ph.D.: Dartmouth Medical School
Molecular Biology of Small Nucleolar RNAs (snoRNAs): A Major Frontier in the Eukaryotic RNA World
Our research is directed at understanding snoRNAs, which comprise the largest population of small, stable RNA in eukaryotic cells. Most snoRNAs fall into two groups, the box C/D and H/ACA families. A few snoRNAs in each family play essential roles in processing (cleavage) of large precursor rRNAs, most likely as chaperones. However, the vast majority function in targeting the major nucleotide modifications in rRNA, i.e., 2'-O-methylation (box C/D snoRNAs) and pseudouridine formation (H/ACA box snoRNAs).
Contributions by our laboratory include: 1) discovery of the rRNA processing function of the U14 snoRNA; 2) genetic characterization of many novel yeast snoRNAs; 3) identification of the family of H/ACA box snoRNAs, and; 4) discovery of the guide functions of snoRNAs in nucleotide modification. Work in progress is devoted to understanding how the processing and guide snoRNA:protein complexes (snoRNPs) mediate their functions, and exploring the potential for using snoRNAs as tools in basic research, biotechnology, and medicine.
We are using snoRNAs as tools in two contexts: 1) methylation of new sites in yeast rRNA, and, 2) as a delivery vehicle for introducing an RNA-cleaving ribozyme to the nucleolus. Methylation can lead to phenotypic defects, providing an effective new approach for functional mapping of RNA. In the ribozyme work, we have successfully localized a hammerhead ribozyme to the nucleolus and cleaved a target RNA with near-perfect efficiency.
Liu, B. and Fournier, M.J. Targeting Methylation snoRNPs to Petidyl Transferase Center Affects Both Ribosome Biogenesis and Translation Efficiency. (in preparation).
Decatur, W.A. and Fournier, M.J. Probing rRNA by snoRNP-Directed Methylation Identifies Several 2'OH's Implicated in tRNA and mRNA Binding. (in preparation).
Liu, B. and Fournier, M.J. 2004. Interference Probing of rRNA with snoRNPs: A Novel Approach for Functional Mapping of RNA In Vivo. RNA 2004: 1130-1141.
Schattner, P., Decatur, W. A., Davis, C. A., Ares, M. Jr., Fournier, M. J., and Lowe, T.M. 2004. Genome-Wide Searching for Pseudouridylation Guide snoRNAs: Analysis of the Saccharomyces cerevisiae Genome. Nucleic Acids Res. 2004 32:4281-4296.
Bertrand, E. and Fournier, M.J. 2004. The snoRNPs and Related Machines: Ancient Devices That Mediate Maturation of rRNA and Other RNAs. pp. 225-261. The Nucleolus (M.O.J. Olson, ed.). Landes Bioscience Publishing
Omer, A.D., Zeische, S., Decatur, W.A., Fournier, M.J., and Dennis, P.P. 2003. RNA-Modifying Machines in Archaea. Mol. Microbiol. 48: 617-629.
King, T.H., Liu, B., McCully, R.R., and Fournier, M.J. 2003. Ribosome Structure and Activity are Altered in Cells Lacking snoRNPs That Form Pseudouridines in the Peptidyl Transferase Center. Mol. Cell 11: 425-435.
Decatur, W.A. and Fournier, M.J. 2003. RNA-Guided Nucleotide Modification of Ribosomal and Other RNAs. A Minireview. J. Biol. Chem. 278: 695-698.
Decatur, W.A. and Fournier, M.J. 2002. rRNA Modifications and Ribosome Function. Trends Biochem. Sci. 27: 344-351.
King, T., Decatur, W., Bertrand, E., Maxwell, E.S. and Fournier, M.J. 2001. A Well-Connected and Conserved Nucleoplasmic Helicase is Required for Production of Box C/D and H/ACA snoRNAs and Localization of snoRNP Proteins. Mol. Cell Biol. 21:7731-7746.
Liu, B., Ni, J. and Fournier, M.J. 2001. Probing RNA In Vivo with Methylation Guide snoRNAs. Methods 23, 276-286.
Zebarjadian, Y., King T., Fournier, M.J., Clarke, L. and Carbon, J. 1999. Point Mutations in Yeast CBF5 can Abolish In Vivo Pseudouridylation of Ribosomal RNA. Mol. Cell. Biol. 19: 7461-7472.
Samarsky, D.A., Ferbeyre, G., Bertrand, E., Singer, R,H., Cedergren, R. and Fournier, M.J. (1999) A Small Nucleolar RNA:Ribozyme Hybrid Cleaves a Nucleolar RNA Target In Vivo with Near-Perfect Efficiency. Proc. Natl. Acad. Sci. USA 96: 6609-6614. [Coverage of this paper] Rossi J.J. (1999) Ribozymes in the nucleolus. Science, 1999 Sep 10;285(5434):1685. Dove A. (1999) Ribozyme, snorbozyme. Nat Biotechnol, 1999 Aug;17(8):738.
Samarsky, D.A. and Fournier, M.J. (1999) A Comprehensive Electronic Database for Yeast Small Nucleolar RNAs. Nucleic Acids Research 27: 161-164.
Samarsky, D.A., Fournier, M.J., Singer, R.H. and Bertrand, E. (1998) The snoRNA Box C/D Motif Directs Nucleolar Targeting and Also Couples snoRNA Synthesis and Localization. EMBO J. 17, 3747-3757.
Samarsky, D.A. and Fournier, M.J. (1998) Functional Mapping of the U3 Small Nucleolar RNA from the Yeast Saccharomyces cerevisiae. Mol. Cell. Biol. 18, 3431-3444.
Ofengand, J. and Fournier, M.J. (1998) The Pseudouridine Residues of Ribosomal RNA: Number, Location, Biosynthesis, and Function. In: Modification and Editing of RNA: The Alteration of RNA Structure and Function. (H. Grosjean and R. Benne, eds.), ASM Press, pp. 229-253.
Ni, J., Tien, A.L. and Fournier, M.J. (1997) Small Nucleolar RNAs Direct Site-Specific Pseudouridine Synthesis in Ribosomal RNA. Cell 89, 565-573.
Balakin, A.G. and Fournier, M.J. (1996) The RNA World of the Nucleolus: Two Major Families of Small RNAs Defined by Different Box Elements With Related Functions. Cell 86, 823-834.