Preliminary Events in Olfaction 
and a Tissue-Specific snRNP Protein 
Michael R. Lemer, M.D., Ph.D. — Associate Investigator 
Dr. Lemer is also Associate Professor in the Department of Internal Medicine at Yale University School of 
Medicine. He obtained his B.A. degree in chemistry from the University of Pennsylvania. He received his 
M.D. degree from Yale University as well as the Ph.D. degree for work done with Joan Steitz on small nu- 
clear ribonucleoproteins (snRNPs). He had an internship in internal medicine at Barnes Hospital, St. 
Louts, and did postdoctoral research in neurobiology at Washington University with Gerald Pischbach 
before returning to Yale. His honors include the Wilson S. Stone Award and the Lee C. Howley, Sr., Prize 
for research in arthritis. 
IN human beings, olfaction is primarily a he- 
donistic sense; among other things, it provides 
most of the enjoyment derived from eating. For 
other animals, however, olfaction is important 
for finding mates and food and avoiding enemies 
and noxious compounds. To study the mecha- 
nisms behind olfaction, we are using as a model 
system the moth Manduca sexta. 
Male moths locate females by their keen ability 
to detect sex pheromones released by females up 
to several miles distant. The "nose" of a moth is 
its antennae. The antennae are covered with fine 
hair-like processes called sensilla. The surface of 
a sensillum is composed of chitin perforated by 
numerous small pores, which open into tubules 
leading into a receptor lymph. Inside each sensil- 
lum and surrounded by the receptor lymph are 
the cilia from olfactory receptor neurons. 
For an air-breathing animal to detect an odor, 
three events must take place. First, the volatile 
chemical in question, which is often quite hydro- 
phobic, must cross an aqueous-based medium — 
in the case of moths, the receptor lymph — to 
reach the cilia. A perfect example of such an 
odorant is bombykal, a l6-chain hydrocarbon 
with an aldehyde group at one end, which is a sex 
pheromone for Manduca. Second, the chemical 
must interact with its receptor. Third, the chemi- 
cal, or at least its action, must be terminated. This 
last point is particularly important in the case of 
pheromones, where real-life working concentra- 
tions are subpicomolar, necessitating that noise 
be kept to a minimum. 
The receptor lymph is inundated with a 15- 
kDa protein called pheromone-binding protein 
(PBP). It is widely hypothesized that PBP is in- 
volved in the translocation of pheromone from 
the pore tubules to the membranes of the cilia. 
We have been characterizing this binding protein 
in Manduca and are currently working on its de- 
velopmental regulation. To facilitate these stud- 
ies we have cloned and sequenced the cDNA en- 
coding it. 
If PBP is responsible for solubilizing and trans- 
porting pheromone to pheromone receptors, 
how do general odorants get to their receptors? 
We have found that the olfactory sensilla for de- 
tecting general odors have two proteins that are 
related to PBP. These proteins, which are ex- 
pressed in both males and females, may be gen- 
eral odorant carriers. Recently we cloned and se- 
quenced cDNA coding for both of these proteins, 
which have been named GOBPs (general odor- 
ant-binding proteins). 
Odor inactivation could be the result of any of 
several processes, ranging from destruction of the 
chemical in question, once it has interacted with 
a receptor, to desensitization of the receptor. A 
developmentally regulated antenna-specific al- 
dehyde oxidase (AOX) has been identified. This 
1 50-kDa enzyme has a strong preference for bom- 
bykal as a substrate as opposed to other alde- 
hydes. As a result of the AOX, the half-life of a 
molecule of pheromone, once it enters a sensil- 
lum, is less than 1 millisecond. 
A Tissue-Specific snRNP Protein 
Messenger RNA splicing is a fundamental pro- 
cess in eukaryotic cells. The precise removal of 
intervening sequences (introns) and the rejoin- 
ing of exons to form an mRNA encoding a specific 
protein are in some ways analogous to making a 
movie. First many scenes are taken. The primary 
RNA transcript made from a DNA template is akin 
to this unprocessed film. Like the film, RNA is 
processed in several ways. For example, a modi- 
fied nucleotide cap structure is placed at the be- 
ginning of the RNA transcript — just as a title and 
headings are placed at the beginning of the film. 
Also, a strip of nucleotides, the poly(A) tail, is 
added to the 3' end of the RNA — as credits are 
added at the end of the film. One of the most 
interesting and basic things that happens to an 
RNA transcript during its maturation is the exci- 
sion of introns and the connection of exons. 
Again, as in movie making, the film that has taken 
many hours to shoot must be edited so that only 
the most important two hours remain. The cellu- 
lar components that perform these splicing reac- 
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