Polypyrimidine tract binding protein leads to formation of delta-FosB, which mediates certain neural and behavioral modifications that occur with addiction.
Researchers at Rosalind Franklin University of Medicine and Science found a mechanism for one of the changes in gene expression that occurs when individuals take addictive drugs.
The study focused on how the primary RNA transcript is processed by splicing to produce a mature transcript. An immediate and prominent alteration that occurs with administration of amphetamine or cocaine is the accumulation in one region of the brain of very stable truncated isoform of the transcription factor FosB, termed delta-FosB, that is produced by alternative splicing of the transcript, the team reports.
delta-FosB mediates some of the neural and behavioral modifications that occur with drug addiction. The results from the study found that a phosphorylated splicing factor, polypyrimidine tract binding protein, promotes intron retention and thereby silences the splicing of fosB. This results in the truncated form of FosB being produced instead of the less-stable, full-length protein.
The findings of this study are published in the September 5th issue of PLoS ONE.
