Spanish researchers discover protein production regulation mechanism

Researchers from Spain and the United States have made a significant discovery about how neurons develop and maintain their identities. The study was conducted on the small worm C. elegans, which is often used in biological research. The findings were published in the journal Genes & Development. The researchers identified a mechanism that enables a single gene, ceh-44, to create two different proteins. This gene is similar to the CUX1 gene found in humans and mice. One protein acts as a transcription factor, crucial for regulating neuronal genes, while the other protein's function is still not known. The lead researcher, Eduardo Leyva Díaz, noted that this genetic setup is also found in vertebrates, suggesting it plays a vital role in neuron development. Neurons have unique structures and do not divide after they are formed. Their identity affects their functions throughout their lifespan. Cells express specific genes to define their activities, and any changes in this process can lead to neurological disorders. The study reveals how neurons maintain their identities through a process called alternative splicing. This process allows a single gene to produce different proteins based on how the RNA pieces are put together. The team discovered that a splicing factor called UNC-75 in C. elegans and CELF in vertebrates controls the production of the neuronal version of the CEH-44 protein. This finding highlights the importance of UNC-75/CELF in regulating neuronal identity by promoting the production of the neuronal protein while preventing the creation of a non-neuronal form. Using the C. elegans model allowed the team to make quick genetic modifications and identify conserved mechanisms in how neurons develop. The study employed advanced techniques such as CRISPR-Cas9 for gene editing and microscopy to analyze the gene expression processes. Moving forward, the researchers plan to explore whether this splicing mechanism is also present in vertebrates and how it impacts neuron circuit formation in the brain. Understanding neuronal identity generation is crucial for uncovering developmental processes in the nervous system and may provide insights into diseases where this identity is disrupted.