Brenda A. Peculis

Associate Professor of Biochemistry

Email:	peculisb@missouri.edu
Phone:	(573) 884-1424
Lab:	(573) 884-3418
Fax:	(573) 884-4812
Office:	11B Schlundt Annex
Mailing Address:	Biochemistry 117 Schweitzer Hall University of Missouri-Columbia Columbia, MO 65211
Research Areas:	RNA processing, RNA stability, RNA turnover, RNA decapping enzymes, snoRNPs required for ribosome biogenesis.

Educational Background

BS	Loyola University Chicago	Chicago, Ill.	Biology
MS	Loyola University Chicago	Chicago, Ill.	Biology
PhD	Johns Hopkins University	Baltimore, Md.	Biology

Research Description

My lab examines RNA metabolism to better understand how molecular events affect the growth rates of cells. Our molecular focus is on RNA processing events, RNA-RNA and RNA-protein interactions that mediate RNA folding and controlled RNA hydrolysis to affect RNA stability in vivo. While some of our assays are in vitro, our goals are to understand how changes in the folding or assembly of specific RNA components affect the ability of a cell to grow and respond to the environment that exists within an organism. We use a variety of model systems to pose questions that can be addressed using different molecular, biochemical, biophysical and biological tools. We can isolate or manipulate individual components of the universally conserved cellular pathway of ribosome biogenesis or other associated pathways to understand the unique roles and identify novel players essential for ribosome biogenesis in eukaryotes.

We have been examining the role of the U8 snoRNA, which is required for ribosome biogenesis which in turn regulates the rate of cell growth and division. . One current focus of the lab is to understand the physiological implications of a novel nuclear protein called X29, found through its high affinity binding to U8 snoRNA. X29, H29 (the human homologue) and the putative homologues in other species including rat, insect and fish, belong to the NUDIX family. These subset of NUcleoside DIphosphatases are nuclear-localized RNA-dependent decapping proteins that requires metal and can remove m7G caps present on the 5-prime end of nuclear RNAs. Our hypothesis is that that in vivo, these nuclear decapping proteins are negative regulators of a variety of nuclear RNAs, including snoRNAs. Thus this protein has the potential to regulate a variety of cellular pathways, including ribosome biogenesis. We propose that this protein in frog, as well as the mammalian and other vertebrate homologues, is a key player in directing nuclear RNA degradation and modulating gene expression. On-going biological, biochemical and biophysical studies of this protein are assisting our examination of the in vivo role of this protein. The crystal structure of the frog X29 protein (below left), with m7GpppG cap analogue and metal bound in the active site (below right) is facilitating structure-based mutagenesis yielding proteins that are being examined on a biochemical level in vitro and which are being examined in vivo for additional functional characterization to understand how this novel nuclear protein functions.

Selected Publications

Cote, C.A., Greer, C.L. and Peculis, B.A. (2002) Dynamic conformational model for the role of ITS2 in pre-rRNA processing in yeast. RNA 8: 786-797.

Ghosh, T., Peterson, B. and Peculis, B.A. (2004) Xenopus U8 Binding Protein is a Conserved Nuclear Decapping Enzyme. Molecular Cell 13: 817-828

Peculis, B.A., Scarsdale, J.N., Wright, H.T. (2004) Crystals of X29, a Xenopus laevis U8 snoRNA binding protein with nuclear decapping activity. Acta Cryst. D. 60:1668-9.

Scarsdale, JN, Peculis, BA, and Wright, HT. (2006) Crystal Structures of U8 snoRNA Decapping Nudix Hydrolase (X29) and its Metal and Cap Complexes. Structure. 14:331-43.

Peculis, B.A., Reynolds, K and Cleland, M. (2007) Metal determines efficiency and substrate specificity of the nuclear NUDIX decapping proteins X29 and H29K (Nudt16). J Biol Chem. 282:24792-805.

Employment Opportunities

Post-Doctoral Opportunities

Electronic submission is encouraged, e-mail to biochemsearch@missouri.edu

Applicants should send CV and names of two references to:
Dr. Brenda Peculis
Postdoctoral Application
Biochemistry
117 Schweitzer Hall
University of Missouri-Columbia
Columbia, MO 65211

RNA processing, RNA stability, RNA turnover, RNA decapping enzymes, snoRNPs required for ribosome biogenesis.