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POST-TRANSCRIPTIONAL CONTROL OF GENE EXPRESSION 
Sandra L. Woun, M.D., Ph.D., Assistant Investigator 
Dr. Wolin's laboratory is interested in understand- 
ing post-transcriptional mechanisms for regulating 
eukaryotic gene expression. In one project, Dr. Wo- 
lin and her colleagues are studying mechanisms that 
regulate the translation of mRNAs into proteins. In a 
second project, they are investigating the structure 
and function of a conserved class of small cytoplas- 
mic ribonucleoprotein particles. 
Translation Mechanisms 
It has long been observed that the movement of 
ribosomes along mRNA during translation is not lin- 
ear with time. Rather, ribosomes pause at discrete 
sites for unknown reasons. Several possible causes 
of ribosome stalling are mRNA sequence and struc- 
ture as well as activities of trans-acting factors in the 
translation reaction. The importance of these factors 
in regulating the movement of ribosomes along the 
mRNA has been relatively unexplored, perhaps be- 
cause of the absence of an assay sensitive enough to 
detect subtle changes in ribosome movement. The 
laboratory has developed and is currently using such 
an assay to probe the dynamics of ribosome move- 
ment during translation. 
A newly revealed slow point in translation initi- 
ation. The laboratory has shown that one major po- 
sition of ribosome pausing, in both reticulocyte and 
wheat germ extracts, is directly over the initiation 
codon of the mRNA. This pausing by fully assembled 
ribosomes appears to represent a slow step in eu- 
karyotic protein initiation that has not been previ- 
ously detected. This slow point in translation is a 
bona fide intermediate in translation, because >50% 
of the ribosomes that pause at this position continue 
to move down the mRNA. By using initiation inhibi- 
tors that are specific for individual steps in transla- 
tion, it has been determined that the first peptide 
bond has been synthesized but has not yet been 
translocated from the A site to the P site of the ribo- 
some. Thus the first elongation factor 2 (EF-2)- 
dependent translocation event appears to be a rate- 
limiting step in the translation of a variety of 
different mRNAs in vitro. Recent studies suggest 
that this slow point in translation also occurs in 
vivo. 
What features of mRNA sequence result in ribo- 
some pausing and frameshifting? Because codon 
usage is strongly correlated with the relative abun- 
dance of the respective tRNA species, it has fre- 
quently been suggested that ribosome pausing oc- 
curs at rare codons. To study this question, the 
laboratory has prepared translation extracts in 
which tRNA molecules and amino acids have been 
removed. By adding back uncharged tRNA and dif- 
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