James Anderson

 

James T. Anderson

Associate Professor
Wehr Life Sciences, 412
(414) 288-1481
E-mail

B.Sc. 1990, Southwest Missouri State University, Springfield, MO
Ph.D. 1994, University of Florida, Gainesville, FL
Postdoctoral Fellow: 1995-2000, National Institutes of Health, Bethesda, MD

 

Genetics and Biochemistry of RNA Surveillance

 

The lab is studying RNA surveillance in the yeast Saccharomyces cerevisiae. Transfer RNA (tRNA) contains the greatest number and diversity of modified nucleotides. Interestingly, the essential function of one such modification, m1A58, in maintaining the stability of tRNAiMet, led to the discovery of a tRNA surveillance mechanism that is now known to be utilized in the surveillance of many cellular RNAs. This RNA surveillance mechanism requires two main complexes: 1) TRAMP, a three subunit complex that modifies RNAs to be eliminated through 3' end adenylation, and 2) The exosome; a multisubunit RNA degrading complex. Our current focus is determining the molecular mechanism of RNA recognition and adenylation by the surveillance complex TRAMP. Presently, there are two main projects in the lab.

1. Genetic and biochemical characterization of mutants in TRAMP subunits, Mtr4 and Air2. We are using an innovative dominant negative genetic screen to identify mutations in Mtr4 and Air2, and studying the effect they have on RNA adenylation and turnover in vitro and in vivo.

2. We have begun to characterize TRAMP in mus musculus (mouse) and are seeking to identify RNA targets of TRAMP using siRNA knockdown of TRAMP subunits in mouse cell lines. We are using modern methodologies such as microarray and deep RNA sequencing to interrogate the accumulation of RNAs under conditions of TRAMP depletion.

The laboratory, which is actively recruiting new graduate students, provides a great opportunity to individuals looking for research experience in the biochemistry and genetics of tRNA processing.

Selected Publications

Huijue, J., Wang, X., Liu, F., Geunther, U.P., Srinivasan, S., Anderson, J.T., and Jankowsky, E. 2011. The RNA helicase Mtr4p modulates polyadenylation in the TRAMP complex. Cell. Jun 10 145(6);890-901.

Chen, C., Huang, B., Anderson, J.T., and Byström, A.S. 2011. Unexpected accumulation of ncm5U and ncm5s2U in a trm9 mutant suggests an additional step in the synthesis of mcm5U and mcm5s2U. PLoS One. Epub 20783. June 7.

Anderson, J.T., and Wang, X. 2009 Nuclear RNA surveillance: no sign of substrates tailing off. Crit Rev Biochem Mol Bio. Jan-Feb: 44(1) 16-24.

Ozanick, S.G., Wang, X., Costanzo, M., Brost, R.L., Boone, C., and Anderson, J.T. 2009. Rex1p deficiency leads to accumulation of precursor initiator tRNAMet and polyadenylation of substrate RNAs in Saccharomyces cerevisiae. Nucleic Acids Res. Jan:37(1): 298-308.

Wang, X., Jia, H., Jankowsky, E., and Anderson, J.T. 2008 Degradation of hypomodified tRNA(iMet) in vivo involves RNA-dependent ATPase activity of the DExH helicase Mtr4p. RNA. Jan;14(1) 107-116.

Kadaba, S., Wang, X., and and Anderson J.T. 2006. Nuclear RNA surveillance in Saccharomyces cerevisiae: Trf4p-dependent polyadenylation of nascent hypomethylated tRNA and an aberrant form of 5S rRNA. RNA March 12(3). 508-521.

Ozanick, S., Krecic, A., Andersland, J., and and Anderson, J.T. 2005. The bipartite structure of the tRNA m1A58 methyltransferase from S. cerevisiae is conserved in humans. RNA. Aug;11(8):1281-90.

Kadaba, S., Krueger, A., Trice, T., Krecic, A.M., Hinnebusch, A.G., and Anderson, J.T. 2004. Nuclear surveillance and degradation of hypomodified initiator tRNAMet in S. cerevisiae. Genes Dev. 18(11): 1227-1240.

Anderson, J.T., Phan, L., and Hinnebusch, A.G. 2000. The Gcd10p/Gcd14p complex is the essential tow-subunit tRNA(1-methyladenosine) methyltransferase of Saccharomyces cerevisiae. PNAS. 97:5173-5178.

Calvo, O., Cuesta, R., Anderson, J.T., Garcia Barrio, M., Hinnebusch, A.G., and Tamame, M. 1999. Gcd14p, a Repressor of GCN4 Translation, Cooperates with Gcd10p and Lhp1p in the Maturation of Methionyl-tRNA in Saccharomyces cerevisiae. Mol. Cell Biol. 19:4167-4181.

Anderson, J.T., Phan, L., Cuesta, R., Carlson, B.A., Asano, K., Pak, M., Björk, G.R., Tamame, M., and Hinnebusch, A.G. 1998. The Essential Gcd10p-Gcd14-p Nuclear Complex is Required for 1-methyladenosine Modification and Maturation of Initiator Methionyl-tRNA. Genes Dev. 12:3650-3662.

 

Awards

Way Klingler Young Scholars Award (2006)

 

Current Students

Yan Li (Ph.D. student)

Alexis Onderak (Ph.D. student)

Fengchao Wang (Ph.D. student)

Dr. Anderson is currently accepting new Ph.D. students into his lab

 



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