Molecular Genetics of RNA Processing and Behavior 
Mutants in this gene, originally identified more 
than 20 years ago, have profound effects on circa- 
dian rhythms of locomotor activity and of eclo- 
sion (emergence of adults from the pupal case) . 
Recently we discovered that the per gene prod- 
ucts, mRNA as well as protein, undergo circadian 
fluctuations in level during the circadian cycle. 
These observations and others indicated that there 
is a feedback loop in which the per protein nega- 
tively affects the level of its own mRNA. Since the 
per mRNA also gives rise to the per protein during 
translation, this putative feedback loop contains 
all of the elements required to define a circadian 
clock, including a substantial (and mysterious) 
delay between the mRNA and protein accumula- 
tion curves. We are studying several aspects of this 
loop in an attempt to confirm (or refute) its im- 
portance to the circadian clock. 
Because no close relatives of the per protein 
with a known biochemical function are found in 
the database, we cannot say for certain what gene 
family it belongs to or what biochemical function 
it serves. We suspect, however, that it is a tran- 
scription factor, or serves to modulate transcrip- 
tion, and that its effect on its own mRNA levels is 
quite direct. A current goal is to test this hypothe- 
sis and to define the biochemical function of the 
per gene product, especially insofar as rhythms 
are concerned. 
With the support of a grant from the National 
Institutes of Health, we are also in the process of 
defining and studying several other genes that af- 
fect rhythms. Although these genes are in a less 
well developed state of examination than the per 
gene, some appear interesting and may provide 
additional insight into clock mechanisms. 
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