Investigating the role of alternative 3’UTRs in G-protein signaling

The striatum, a region of the brain responsible for motor control and reward processing, plays a critical role in various neurological disorders, including Parkinson's disease, Huntington's disease, and addiction. Gnal encodes the heterotrimeric G-protein stimulatory alpha subunit, Gαolf. Gαolf is highly expressed in the striatum, a brain region that is highly relevant to psychosis and psychostimulant drug action. The Gγ7 protein is also enriched in the striatum, where we have previously shown that Gγ7 protein is required at the posttranscriptional level for the hierarchical assembly of the striatal-specific Gαo lfβ2γ7 heterotrimer, which represents the rate-limiting step for cAMP production in striatal D1R and D2R-expressing neurons in the D1 dopamine and A2a adenosine pathways.
Multiple transcripts with variable 3’ UTRs are produced from the Gng7 gene. Previous studies have shown that genes with these characteristics are post-transcriptionally regulated and can be subcellularly localized. Thus, we hypothesized that the γ7 transcripts with variable 3’UTRs act as signaling organizers that regulate the abundance and/or subcellular localization required for preferential assembly and specialized signaling by Golf heterotrimer in the brain. Our findings showed that striatal-enriched γ7 transcripts are post-transcriptionally regulated by virtue of regulatory elements outside of the coding region that bind to its long 3’UTR. These regulatory elements are responsible for translational repression of the γ7 protein. The different length 3’UTRs of the γ7 transcripts 1 and 3 allow for subcellar localization in the nuclei and the neuropil respectively.