Judith A. Jaehning, Ph.D.

Professor of Biochemistry & Molecular Genetics

Department of Biochemistry and Molecular Genetics
University of Colorado Health Sciences Center
Campus Box B121
4200 East Ninth Avenue
Denver, Colorado 80262

Office Phone: 303.315.3004
FAX: 303.315.3326
Judith.Jaehning@uchsc.edu

EDUCATION/EXPERIENCE

HONORS AND AWARDS

PROFESSIONAL ACTIVITIES

LAB PERSONNEL

Research Interests

My laboratory studies yeat RNA polymerases and their accessory factors. In particular, we are working with the nuclear RNA polymerase II in a selective transcription extract which is responsive to transcriptional activators and repressors. We are also studying the structure of the mitochondrial RNA polymerase, and its roles in regulating mitochondrial transcription and in coordinating gene expression between the nucleus and the mitochondrion.

We have identified a novel collection of transcription factors associated with RNA polymerase II. The complex appears to play an important role in the expression of subsets of yeast genes in response to MAP-kinase signalling pathways. Factors in the complex are required for proper expressio of genes during the cell cycle. The complex also may be involved in the developmental program of meiosis and sporulation in yeast. Recently homologues of the factors in the RNA polymerase II complex have been identified in the human genome. This may mean that human cells also use multiple forms of RNA polymerase II to differentially regulate subsets of genes.

We are currently studying interactions of the factors in the complex with each other and the RNA polymerase as well as characterizing several other gene products which appear to play a role in RNA polymerase II transcription.

Remarkably little is known about mitochondrial transcription. The yeast enzyme is the only one with a defined structure. We have shown that this RNA polymerase is composed of two nuclear encoded subunits, a catalytic core and a specificity factor required for recognition of the simple promoter-ATATAAGTA. The core polymerase resembles the simple enzymes from phage T7 and T3; the specificity factor shares similarity to bacterial sigma factors. We have found that like the bacterial sigma factors, the mitochondrial specificity factor is released from the transcription complex shortly after initiation. We have isolated a large collection of point mutations in the sigma-like specificity factor. We have used these to map the interface between the two subunits of the RNA polymerase andare currently using the mutationa to understand how this simple enzyme recognizes the promoter and initiates transcription.

Mitochondrial transcription is subject to glucose repression. We have demonstrated that the change is due to a change in the rate of transcription, not to changes in the copy number of the mitochondrial DNA, We have concluded that regulation must involve factors in addition to the RNA polymerase regulated by nuclear genes. We are studying mutations that affect glucose repression to reveal the control mechanisms.

Selected Publications

• P.F. Cliften, J.-Y. Park, B.P. Davis, S-H. Jang, and J.A. Jaehning, Identification of Three Domains Essential for Interaction Between a Sigma-Like Factor and Core RNA Polymerase. Genes & Dev. 11:2897-2909 (1997). [Abstract]

• M. Chang and J.A. Jaehning, A Multiplicity of Mediators: Alternative Forms of Transcription Complexes Communicate with Transcriptional Regulators. Nucleic Acids Research, 25:4861-4865 (1997). [Abstract]

• M. Chang, D. French-Cornay, H. Klein, C. Denis and J.A. Jaehning. A Complex Containing RNA Polymerase II, Paf1p, Cdc73p, Hpr1p and Ccr4p Plays a Role in Protein Kinase C Signaling. Mol. Cell. Biol., 19:1056-1067 (1999). [Abstract]

• P.F. Cliften and J.A. Jaehning, DNA Dependent RNA Polymerases, in Encyclopedia of Molecular Biology, (T. Creighton, ed.) John Wiley, NY (1999).

• P.F. Cliften and J.A. Jaehning, Sigma Factors, in Encyclopedia of Molecular Biology, (T. Creighton, ed.) John Wiley, NY (1999).

• P.F. Cliften, S-H. Jang and J.A. Jaehning. Identifying a Core RNA Polymerase Surface Critical for Interactions with a Sigma-Like Specificity Factor. 20:7013-7023, Mol. Cell. Biol. (2000) [Abstract]

• C.L. Mueller, T.M. Washburn and J.A. Jaehning, Ctr9, Rtf1 and Leo1 are Components of the Paf1/RNA polymerase II complex. In press Mol. Cell. Biol. (2002)

• J.L. Betz, T.M. Washburn, S.E. Porter, and J.A. Jaehning, Expanded Functional Role of the Yeast Paf1p/RNA polymerase Ii Complex Deduced from Phenotypic Analysis. Submitted.
  

• S.E. Porter, D. French-Cornay, J.L Betz, T M.Washburn and J.A. Jaehning. The Yeast Paf1/RNA Polymerase II Complex is Required for Full Expression of a Subset of Cell Cycle Regulated Genes. Submitted.

• M. Karlok, B. Davis. S-H. Jang and J.A. Jaehning, Mutations in the Yeast Mitochondrial RNA Polymerase Specificity Factor Mtf1 Lead to Altered Promoter Recognition. In preparation.
  

Bibliography