Jeffrey Wilusz
Professor

Phone: 491-0652
Fax: 491-1815
Email: Jeffrey.Wilusz@ColoState.EDU
Office: B321 Microbiology Building
Lab: B325 Microbiology Building
Lab Website: http://www.cvmbs.colostate.edu/mip/wiluszlab

Degrees

B.S., Cook College of Rutgers University
PhD, Duke University

Research Interests

The current focus of my research is to decipher the mechanisms of mRNA turnover in mammalian cells and how this machinery influences a viral infection. In 1999 we reported the development of an in vitro assay using HeLa cell cytoplasmic S100 extracts that faithfully reproduces many aspects of regulated deadenylation/turnover of mammalian mRNAs. This system has become the centerpiece of our research efforts. To date, we have used this in vitro approach to extensively characterize mRNA decay in human cells. Some notable findings include

Identified PARN as the major deadenylase in HeLa extracts.

Discovered a novel, functionally important interaction between PARN and the mRNA cap, suggesting that recognition of both the 5’ and 3’ ends in important to initiate mRNA decay.

Isolated a novel, Dcp1/2p-like mRNA decapping activity in mammalian extracts that is regulated by cap binding proteins and the poly(A) tail.

Identified the 3’-to-5’ decay mediated by a complex of exonucleases called the exosome as the major route of mRNA decay following deadenylation in Hela cytoplasmic extracts.

Uncovered a sequence-specific role for the exosome in rapid mRNA turnover mediated by AU-rich regulatory elements commonly found in the 3’ UTR of short-lived mRNAs.

• Discovered novel interactions between viral RNAs and the host cell mRNA decay factors

Projects that are currently ongoing in my lab include:

Assessing how transcripts produced by cytoplasmic RNA viruses evade the mRNA turnover machinery in order to gain additional insights into viral-host interactions.

Screening for small molecules that enhance decay of viral RNAs – these may represent novel therapeutics.

Investigating the role of nucleophosmin, a protein that we discovered to be selectively deposited on mRNAs as a result of the polyadenylation event, in post-transcriptional control of gene expression.

In collaboration with Dr. Carol Wilusz:

Identification and characterization of the enzymes and factors responsible for regulated deadenylation in mammalian cells. We are particularly interested in the role of CUG-BP in this process and the potential influence of the role of mis-regulated deadenylation on the pathogenesis of myotonic dystrophy

Selected Publications

Pub Med for Wilusz J.

Sánchez-Vargas I, Scott JC, Poole-Smith BK, Franz AW, Barbosa-Solomieu V, Wilusz J, Olson KE, Blair CD. Dengue virus type 2 infections of Aedes aegypti are modulated by the mosquito's RNA interference pathway. PLoS Pathog. 2009 5(2):e1000299.

Wilusz J. RNA stability: is it the endo' the world as we know it? Nat Struct Mol Biol. 2009 16:9-10.

Zhang, L., Lee, J.E., Wilusz, J., Wilusz, C.J. The RNA-binding protein CUGBP1 regulates stability of tumor necrosis factor mRNA in muscle cells: implications for myotonic dystrophy. J Biol Chem. 2008; 283:22457-63.

Garneau, N.L., K. Sokoloski, M. Opyrchal, C.P. Neff, C.J. Wilusz, and J. Wilusz. The 3' untranslated region of sindbis virus represses the deadenylation of viral transcripts in mosquito and mammalian cells. J. Virol. 2008; 82:880-92

Bergman, N, Moraes KCM, Anderson, J.R., Zarc, B., Kambach, C, Schneider, R.J., Wilusz, C.J. and Wilusz J. Lsm proteins bind to and stabilize RNAs containing 5' poly(A) tracts. Nature Struct Mol. Biol., 14: 824-831, 2007.

Garneau, N.L., J. Wilusz and C.J. Wilusz The highways and byways of mRNA decay. Nature Reviews Mol and Cell Biol., 8: 113-126, 2007.

Sokoloski, K.J., Wilusz, C.J. and Wilusz J. Viruses: overturning mRNA turnover. RNA Biology, 3: 140-144, 2006.

Moraes, K.C., Wilusz, C.J. and Wilusz, J. CUG-BP binds to RNA substrates and recruits PARN deadenylase. RNA, 12: 1084-1091, 2006.

Palaniswamy, V., Moraes, K.C., Wilusz, C.J. and Wilusz, J. Nucleophosmin is selectively deposited on mRNA during polyadenylation. Nature Struct. Mol. Biol. 13: 429-435, 2006.

Opyrchal, M., Anderson, J.R., Sokoloski, K., Wilusz, C.J. and Wilusz, J. A cell-free mRNA stability assay reveals conservation of the enzymes and mechanisms of mRNA decay between mosquito and mammalian cell lines. Insect Biochem Mol Biol, 35: 1321-1334, 2005.