The sense of smell in mammals is extraordinary, allowing them to distinguish a trillion different scents. Each of the millions of nerve cells in the mammalian nose is equipped with specific odor-chemical receptors encoded in the genome, enabling them to detect and identify various odors. Previous research has shown that sensory neurons in the nose are uniquely tuned to detect specific odorants, such as ethyl vanillin from vanilla or limonene from lemons. However, the mechanism by which these sensory cells in the nose choose their receptors has remained a mystery until now.
A team of scientists led by researchers at Columbia’s Zuckerman Institute has discovered a previously unknown mechanism in mice that explains how each sensory cell in mammalian noses becomes specialized to detect a specific odor chemical. The mechanism involves the genetic molecule RNA, which plays a crucial role in the process.
The study, published in the journal Nature, reveals that the refining process takes place within the nucleus of each olfactory neuron, where the cell’s chromosomes and genes are located. In a competition between olfactory receptor genes, the genes undergo a process of elimination, ultimately resulting in the selection of a single gene that determines the cell’s sensitivity to a specific odorant.
In their research, the team uncovered the details of the final stage of this selection process, when the winning gene emerges from the pool of finalists. This process involves a complex interplay of various molecular characters, including gene-regulating molecules that either enhance or suppress the expression of specific genes. Additionally, another set of molecules reshapes portions of the genome, favoring the expression of certain receptor genes.
The researchers have named these reshaping molecules “Greek Islands” due to their resemblance to islands in the Aegean Sea. The spatial organization of the genome in the nucleus plays a crucial role in the expression of olfactory receptor genes, with changes in this structure affecting which genes are turned on or off.
According to the researchers, their data from mouse studies point to RNA as the key molecule in the gene-choosing mechanism of the olfactory system. While RNA is primarily known for its role in translating genetic code into functional proteins, the researchers found evidence suggesting that RNA also plays a role in altering the genome’s architecture, boosting the expression of one olfactory receptor gene while suppressing others.
Although there are still gaps in our understanding of how the genome controls the sense of smell, the researchers believe that the overall picture is becoming clearer. The process starts with maturing olfactory cells expressing multiple receptor genes, with gene-regulating molecules and complexes converging at specific genomic hubs. Then, RNA narrows down the selection to a single gene, with the hub that produces the highest amount of RNA winning the competition. Meanwhile, RNA from that hub may also reach other hubs and cause changes in the genome that inhibit gene expression, resulting in mature olfactory neurons, each bearing a single odorant receptor.
The scientists acknowledge that we have only scratched the surface of what is happening within a cell’s nucleus. They emphasize the need for further research to fully unravel the remaining mysteries of the olfaction puzzle.
The study’s authors include Ariel D. Pourmorady, Elizaveta V. Bashkirova, Andrea M. Chiariello, Houda Belagzhal, Albana Kodra, Rachel Duffié, Jerome Kahiapo, Kevin Monahan, Joan Pulupa, Ira Schieren, Alexa Osterhoudt, Job Dekker, Mario Nicodemi, and Stavros Lomvardas.
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Source: Coherent Market Insights, Public sources, Desk research
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