Faculty in the Department of Molecular Biosciences

Dean A. Stetler Ph.D., Kansas, 1980 Associate Professor 3043 Haworth (785) 864-3549; email: dstetler@ku.edu RNA polymerase I (RNAPI), a complex enzyme composed of 9 subunits, is responsible for the transcription of the rRNA genes. In addition to its importance in transcription, RNAPI is also of interest because of its being targeted by autoantibodies produced by individuals with systemic lupus erythematosus (SLE). Anti-RNAPI antibodies were first demonstrated by this laboratory in both the sera and urine of SLE patients and the relative quantities of the urinary antibodies were found to correlate with severity of the disease. The lab is investigating the possibility of utilizing a urine test for anti-RNAPI antibodies (or other autoantibodies) to monitor SLE disease status, allowing micromanagement of drug dosage and better management of the disease. The lab recently cDNA cloned the largest subunit (S1) of human RNAPI and mapped the gene to chromosome 2. Determination of the position of the gene on this chromosome and identification of restriction fragment length polymorphisms, which will allow determination of the significance of particular RNAPI(S1) alleles to the SLE disease process, is a current effort in the lab. The cDNA cloning of human RNAPI(S1) revealed the existence of alternative forms of RNAPI(S1) mRNA produced by alternative splicing. We are in the process of determining whether these alternatively spliced mRNAs are translated into alternative S1 proteins and, if so, whether they are assembled into RNA polymerases with distinct characteristics.

Representative Publications

Picking, W.L., C. Smith, R. Petruci, J. Scheffel, J.D. Levich, and D. Stetler. 1990.

Anti-RNA polymerase I antibodies in the urine of SLE patients. J. Rheumatol. 17:1308-1313.

Stetler, D.A., D. Signorelli, J. Neil, S. Brady, R. Lottes, and J.C. Brown. 1992.

Anti-RNA polymerase I antibodies in the sera of MRL lupus mice at the initial stages of disease are directed primarily against phosphorylation-dependent epitopes. Autoimmunity 12:29-36.

Rombach, E., D.A. Stetler, and J.C. Brown. 1992.

Rabbits produce SLE-like anti-RNA polymerase I and anti-DNA autoantibodies in response to immunization with either human or murine SLE anti-DNA antibodies. Autoimmunity 13:291-302.

Rombach, E., D.A. Stetler, and J.C. Brown. 1993.

Induction of an anti-Fab, anti-DNA, and anti-RNA polymerase I autoantibody response network in rabbits immunized with SLE anti-DNA antibody. Clin. Exp. Immunol. 94:446-472.

Wang, D., and D.A. Stetler.

Molecular cloning and identification of an alternative form of the largest subunit of human RNA polymerase I (in preparation).

Thurm, C.W., T.L. Cooley, G. Cherry, D.J. Bednarczyk, J.C. Brown, and D.A. Stetler.

Immunization with the largest subunit of RNA polymerase I induces SLE-like anti-DNA antibodies (in preparation).

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