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Postdoctoral Fellowship -transcription in S. pombe

Richard J. Maraia maraiar at exchange.nih.gov
Mon Aug 17 17:54:53 EST 1998

Available to U.S. citizens and permanant residents
Eukaryotic Gene Expression
National Institutes of Health

Our labortaory has shown that while the assembly of a gene-specific
transcription initiation complex is a key determinant of eukaryotic gene
expression, control can also occur at the levels of transcription
termination and reinitiation.  We have focused on the human La protein,
a RNA-binding phosphoprotein originally discovered as an autoantigen in
patients suffering from autoimmune disorders such as Systemic Lupus
Erythematosus.  La protein recognizes the 3’ oligo(U) ends of RNA
polymerase III transcripts.  This oligo(U) motif represents a RNA copy
of the termination signal in DNA, oligo(dT), that causes transcriptional
termination by pol III.  We have shown that La acts as a transcript
release factor that facilitates transcriptional termination and
reinitiation by pol III.  As a RNA-binding protein that remains
associated with nascent pol III transcripts after their synthesis, La
also controls the posttranscriptional processing of these RNAs.  We have
shown that phosphorylation and dephosphorylation of La on serine 366 can
regulate and coordinate transcriptional and posttranscriptional steps in
RNA biogenesis.  
	Ongoing studies in this laboratory make use of a newly developed system
in the fission yeast S. pombe that was engineered to allow examination
of pol III transcriptional termination and the role of the La protein in
this process and in tRNA biogenesis in general.  A tRNA opal suppressor
capable of suppressing a nonsense codon in the mRNA encoding a
colorimetric metabolic marker (Ade6-704) is employed.  This system is
currently being used to identify and dissect genetic regulatory pathways
that are important for tRNA biogenesis.  Intracellular signals that can
integrate the phosphorylation status of La with pathways related to cell
proliferation will be examined.  Our goal is to use information gained
from this system to advance understanding of gene regulation and cell
growth in more complex organisms including humans.  
	Selected publications from this laboratory are: (1) Fan et al., 1998. 
Mol.  Cell Biol.  18:3201-3211., (2) Fan et al., 1997.  Cell
88:707-715.  (3) Goodier et al., 1997.  Mol.  Cell Biol.  17:5823-5832. 
(4) Maraia, R.  J.  1996.  PNAS, USA 93:3383-3387.  
	Queries must include a statement that links your interest in this
position to your previous experience, your C.V., the names and (email)
addresses and telephone numbers of three references.  Send to Richard
J.  Maraia, MD, Chief, Unit on Molecular and Cell Biology, LMGR. 
E-mail: maraiar at exchange.nih.gov.  FAX: 301 480-6863.  Postal address:
MSC-2753 9000 Rockville Pike, Bethesda, MD 20892.


Richard J. Maraia, MD
Chief, Section on Molecular and Cell Biology
Laboratory of Molecular Growth Regulation
National Institute of Child Health
    and Human Development
National Institutes of Health
6/516   MSC-2753
9000 Rockville Pike 
Bethesda, MD 20892
Phone: 301 402-3567
Fax: 301 480-6863

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