MY LABORATORY SUDIES YEAST 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.
Representative Publications:
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).
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. in press, Mol. Cell. Biol.
(2000)
C.L. Mueller, T.M. Washburn and J.A. Jaehning, Ctr9, Rtf1
and Leo1 are Components of the Paf1/RNA polymerase II
complex. Mol. Cell. Biol. 22:1971-1980(2002)
M.A. Karlok,. S-H. Jang and J.A. Jaehning, Mutations in
the Yeast Mitochondrial RNA Polymerase Specificity Factor,
Mtf1, Verify its Essential Role in Promoter Utilization.
(2002) J. Biol. Chem. in press.
S.E. Porter, , T M.Washburn, M. Chang and J.A. Jaehning.
The Yeast Paf1/RNA Polymerase II Complex is Required for
Full Expression of a Subset of Cell Cycle Regulated Genes.
(2002), Euk. Cell. in press.
J.L. Betz, T.M. Washburn, S.E. Porter, and J.A.
Jaehning, Phenotypic Analysis of Paf1/RNA Polymerase II
Complex Mutations Reveals Connections to Cell Cycle
Regulation, Protein Synthesis and Lipid and Nucleic Acid
Metabolism. (2002) Molecular Genetics and Genomics, in
press.
M. Matsunaga and J.A. Jaehning, Intrinsic Promoter Recognition by a “Core” RNA polymerase. J. Biol. Chem. 279(43):44239-44242 (2004)
S.E. Porter, K.L. Penheiter and J.A. Jaehning, Separation of the Paf1 Complex from RNA Polymerase II Results in Changes in its Subnuclear Localization. Eukaryotic Cell, 4(1):209-20 (2005).
K.L. Penheiter, T.M. Washburn, S.E. Porter, M.G. Hoffman and J.A. Jaehning,A Post-Transcriptional Role for the Yeast Paf1-RNA Polymerase II ComplexRevealed by Identification of Primary Targets. Molecular Cell, 20:213-223 (2005).
E.A. Amiott and J.A. Jaehning, Mitochondrial Transcription is Regulated viaan ATP “Sensing Mechanism That couples RNA Abundance to Respiration.Molecular Cell, 22:329-338 (2006).
O. Rozenblatt-Rosen, K.M. Nordick, S. Kaneko, M.G. Hoffman, S.J. Nannepaga,T. Sugimoto, C.M. Hughes, J.L. Manley, M.G. Meyerson, J.A. Jaehning, ThePaf1 Complex Facilitate the Association of Polyadenylation Factors with RNAPolymerase II, Submitted.
E. A. Amiott and J.A. Jaehning, The Importance of the +2 Nucleotide forInitiation by the Mitochondrial RNA Polymerase, Submitted.
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