The researchers found that each variable exon is under the regulatory control of its own promoter (a DNA sequence where RNA polymerase binds to initiate transcription of the gene into pre-mRNA). Once transcribed, the pre-mRNA transcript then predominantly undergoes an intramolecular reaction, known as "cis-splicing," whereby a variable exon is cut out and joined, or "spliced," to the constant region of that same pre-mRNA transcript. Ultimately, this process enables a neuron to manipulate the Pcdh gene structure to generate a number of mRNAs, each containing different variable regions, which will each be translated into a unique Pcdh protein.

This work establishes that through the use of multiple promoters and cis-splicing, individual neurons are able to express distinct combinations of Pcdh genes, and, in turn, proteins. Further work will delineate how the differential expression of Pcdh proteins may underlie the specificity of neural connectivity.

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Contact: Heather Cosel
coselpie@cshl.org
Cold Spring Harbor Laboratory
31-Jul-2002