Jeffrey Wilusz
Professor

Phone: 491-0652
Fax: 491-0603
Email: Jeffrey.Wilusz@ColoState.EDU
Office: B106 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
  1. Identified PARN as the major deadenylase in HeLa extracts.
  2. 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.
  3. Isolated a novel, Dcp1/2p-like mRNA decapping activity in mammalian extracts that is regulated by cap binding proteins and the poly(A) tail.
  4. 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.
  5. 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.

• Projects that are currently ongoing in my lab include:
  1. 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
  2. Assessing how transcripts produced by cytoplasmic RNA viruses evade the mRNA turnover machinery in order to gain additional insights into viral-host interactions.
  3. 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.
  4. Elucidating new roles for Lsm complexes in gene expression. We have, for example, demonstrated that Lsm complexes are associated with RNA stabilization mediated by 5' poly(A) tracts found on poxvirus transcripts.
  5. Identification and characterization of novel elements that mediate 3' end processing in mammalian cells.

Selected Publications

Pub Med for Wilusz J.

• Wilusz, C.J. and Wilusz J. New ways to meet your (3') end-oligouridylation as a step on the path to destruction. Genes & Development, In Press, 2008.
• 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., In Press. 2008
• 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.
• Moraes, K.C., Wilusz, C.J. and J. Wilusz. CUG-BP and 3' UTR Sequences Influence PARN-Mediated Deadenylation in Mammalian Cell Extracts. Genet. Mol. Biol., 30, 646-655. 2007
• Wilusz, C.J. and J. Wilusz HuR-SIRT: The hairy world of posttranscriptional control. Molecular Cell, 25: 485-487, 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.
• Anderson,J.R., Mukherjee,D., Muthukumaraswamy,K., Moraes, K.C.M., Wilusz, C.J. and Wilusz, J. Sequence-Specific RNA Binding Mediated by the RNase PH Domain of Components of the Exosome. RNA 12,1810-1816, 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.
• Wilusz, C.J. and Wilusz, J. Eukaryotic Lsm proteins: lessons from bacteria. Naure. Struct. Mol. Biol. 12: 1031-1036, 2005.
• 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.