Biochemistry and Molecular Biology
Penn State Science
You are here: Home › Directory › Craig Cameron
Craig Cameron

Craig Cameron

Main Content

  • Professor of Biochemistry and Molecular Biology
  • Eberly Chair in Biochemistry and Molecular Biology
201 Althouse Laboratory
University Park, PA 16802
Email: cec9@psu.edu
Phone: (814) 863-8705
Download as vCard

Websites

Research Interests

RNA polymerases and RNA-binding proteins in viral infection and mitochondrial disease

Research Summary

RNA Polymerases and RNA-binding Proteins in Viral Infection and Mitochondrial Disease

Since its inception, the primary goal of this laboratory has been development of strategies to treat or to prevent infections by RNA viruses.  We have used poliovirus and hepatitis C virus (HCV) as our primary model systems.  Our expertise in virology, biochemistry and mechanistic enzymology brings a unique combination of intellectual and technical resources to the study of RNA viruses.  Our initial focus was the viral RNA-dependent RNA polymerase (RdRp).  In particular, we were interested in the kinetic, thermodynamic and structural basis for fidelity of nucleotide incorporation, a topic of considerable importance not only for accurate maintenance, transmission and expression of genetically encoded information but also for targeting the RdRp for antiviral therapy.  These studies have led to exciting discoveries that have moved the lab into many new areas, including enzyme dynamics, vesicular trafficking, innate immunity, vaccine development and mitochondrial molecular biology.  Our work is highly collaborative and includes research teams from academia (local, national and international), government and industry.  We currently have projects in the following areas:  RNA-dependent RNA polymerase mechanism, Viral attenuation and vaccine development, Picornavirus genome replication, Biochemical mechanisms and biological functions of HCV NS3 and NS5a proteins, Mitochondrial transcription and disease, and Lethal mutagenesis as an antiviral strategy.

 

Cameron figure1

Model for formation of picornavirus genome replication and packaging complexes. In a normal cell, COPII-coated vesicles originate from the ER.  These vesicles can be tethered to other COPII-coated vesicles and eventually fuse. In a picornavirus-infected cell, viral protein 2BC hijacks the COPII-coated vesicles and these 2BC-COPII-coated vesicles become eRCs that serve for early replication. As the concentration of viral protein 3CD increases, eRCs are transformed to lRCs which ultimately give rise to packaging complexes.



Cameron Figure 2

 

Hypothetical model for human mitochondrial transcription cycle. (a) Formation of the pre-initiation complex may occur with factors and polymerase interacting once bound to DNA (pathway I), prior to associating with DNA (pathway II) or some combination. (b) Control region for mitochondrial transcription: +1 with (numbers), transcription start sites in mtDNA; shaded rectangles, putative mtTFA-binding sites (TFA BS); circles, IPR sites similar to canonical TFA BS. (c) The pre-initiation complex on LSP is stable and requires both h-mtTFA and h-mtTFB2, unlike that on HSP1. Formation of the open complex represents the primary rate-limiting step on linear templates. Promoter-specific, post-initiation events limit formation of the elongation complex. These events are promoter specific. This post-initiation control could reflect remodeling of factor-factor, factor-polymerase and/or polymerase-RNA/DNA interactions. Elongating polymerase likely functions without factors, as factors and template can act catalytically.

Selected Publications

Journal Articles

  • Shutt, T.E., Cotney, J., Surovtseva, Y., Cameron, C.E. and Shadel, G.S. (2010). Promoter-specific initiation of mitochondrial transcription in the absence of h-mtTFA/Tfam reveals an expanded dynamic range available for regulation of human mitochondrial gene expression. Proc. Natl. Acad. Sci (USA) 107, 12133-8.
  • Hsu, N.-Y., Ilnytska, O., Belov, G., Santiana, M., Chen, Y.-H., Takvorian, P., Pau, C., van der Schaar, H., Kaushik-Basu, N., Balla, T., Cameron, C.E., Ehrenfeld, E., van Kuppeveld, F.J.M. and Altan-Bonnet, N. (2010) Viruses reorganize secretory pathway to form organelles with specific lipid microenvironment for RNA replication. Cell 141, 799-811.
  • Lodeiro, M.F., Uchida, A.U., Reynolds, S.L., Moustafa, I.M., Arnold, J.J. and Cameron, C.E. (2010). Identification of multiple rate-limiting steps during the human mitochondrial transcription cycle in vitro. J. Biol. Chem. 285, 16387-402.
  • Oh, H.S., Pathak, H.B., Goodfellow, I.G., Arnold, J.J., and Cameron, C.E. (2009). Insight into poliovirus genome replication and encapsidation obtained from studies of 3B-3C cleavage site mutants. J. Virol.  83, 9370-9387.
  • Castro, C., Smidansky, E.D., Arnold, J.J., Maksimchuk, K.R., Moustafa, I., Uchida, A., Götte, M., Konigsberg, W. and Cameron, C.E. (2009). Nucleic acid polymerases employ a general acid for nucleotidyl transfer. Nat. Struct. Mol. Biol. 16, 212-8.
  • Arias, A., Arnold, J.J., Sierra, M., Smidansky, E.D., Domingo, E. and Cameron, C.E. (2008). Determinants of RNA-dependent RNA polymerase (in)fidelity revealed by kinetic analysis of the polymerase encoded by a foot-and-mouth disease virus mutant with reduced sensitivity to ribavirin. J. Virol. 82, 12346-55.
  • Pathak, H.B., Oh, H.S., Goodfellow, I.G., Arnold, J.J., and Cameron, C.E. (2008). Picornavirus genome replication: Roles of precursor proteins and rate-limiting steps in oriI-dependent VPg uridylylation. J. Biol. Chem. 283, 30677-88.
  • Amero, C., Arnold, J.J., Moustafa, I., Cameron, C.E. and Foster, M.P. (2008). Identification of the oriI-binding site of PV 3C by using NMR spectroscopy. J. Virol. 82, 4363-70. Epub 2008 Feb 27.
  • Graci, J.D., Too, K., Smidansky, E.D., Edathil, J.P., Barr, E.W., Harki, D.A., Galarraga, J.E., Bollinger, J.M., Jr., Peterson, B.R., Loakes, D., Brown, D.M. and Cameron, C.E. (2008) Lethal mutagenesis of picornaviruses with N6-modified purine nucleoside analogues. Antimicrob. Agents Chemother. 52, 971-9. Epub 2008 Jan 7.
  • Nallagatla, S.R., Hwang, J., Toroney, R., Zheng, X., Cameron, C.E. and Bevilacqua, P.C. (2007) 5’-Triphosphate-dependent activation of PKR by RNAs with short stem-loops. Science 318, 1455-8.
  • Castro, C., Smidansky, E., Maksimchuk, K.R., Arnold, J.J., Korneeva, V.S., Gotte, M., Konigsberg, W., and Cameron, C.E. (2007). Two proton transfers in the transition state for nucleotidyl transfer catalyzed by RNA- and DNA-dependent RNA and DNA polymerases. Proc. Natl. Acad. Sci (USA). 104, 4267-72.
  • Vignuzzi, M., Stone, J.K., Arnold, J.J., Cameron, C.E., and Andino, R. (2006). Genomic diversity in a viral population determines fitness, tissue tropism and pathogenesis. Nature 439, 344-8. Epub 2005 Dec 4.


Review Articles

  • Cameron, C.E., Moustafa, I.M. and Arnold, J.J. (2009). Dynamics: The missing link between structure and function of the viral RNA-dependent RNA polymerase? Curr. Opin. Struct. Biol. 19,768-74.
  • Raney, K.D., Sharma, S.D., Moustafa, I.M., and Cameron, C.E. (2010). Hepatitis C virus non-structural protein 3 (HCV NS3): A multifunctional antiviral target. J. Biol. Chem. 285, 22725-31.
  • Cameron, C.E., Oh, H.S. and Moustafa, I.M. (2010). The expanding role of P3 proteins in the poliovirus lifecycle. Future Microbiol. 5, 867-81.


Book Chapters

  • Smidansky, E., Arnold, J.J., Sholders, A., Peersen, O.B., and Cameron, C.E. (2008) Nucleic acid polymerase fidelity and viral population fitness. In Origin and Evolution of Viruses. Domingo, E., Parrish, C., and Holland, J.J. eds.  Academic Press (Elsevier), London, pp. 135-160.
  • Ng, K.K., Arnold, J.J., and Cameron, C.E. (2008). Structure-function relationships among RNA-dependent RNA polymerases.  In Current Topics in Microbiology and Immunology. Paddison P., and Vogt, P., eds. Springer Publishers, NY, pp. 137-156.


Books

  • Cameron, C.E., Götte, M., and Raney K.D. (2009). Viral Genome Replication. Springer Publishers, NY.