Polypyrimidine tract-binding protein 1 regulates the alternative splicing of dopamine receptor D2.
Dopamine receptor D(2) (DRD2) has two splicing isoforms, a long form (D2L) and short form (D2S), which have distinct functions in the dopaminergic system. However, the regulatory mechanism of the alternative splicing of DRD2 is unknown. In this study, we examined which splicing factors regulate the expression of D2L and D2S by over-expressing several RNA-binding proteins in HEK293 cells. In a cellular splicing assay, the over-expression of polypyrimidine tract-binding protein 1 (PTBP1) reduced the expression of D2S, whereas the knockdown of PTBP1 increased the expression of D2S. We also identified the regions of DRD2 that are responsive to PTBP1 using heterologous minigenes and deletion mutants. Our results indicate that PTBP1 regulates the alternative splicing of DRD2. Considering that DRD2 inhibits cAMP-dependent protein kinase A, which modulates the intracellular localization of PTBP1, PTBP1 may contribute to the autoregulation of DRD2 by regulating the expression of its isoforms.
Department of Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo, Tokyo, Japan.
Toshikazu
T
Sasabe
Eugene
E
Futai
Shoichi
S
Ishiura
D017398:Alternative Splicing / Q000235:genetics*; D045744:Cell Line, Tumor; D065127:Dopamine D2 Receptor Antagonists; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D034441:Heterogeneous-Nuclear Ribonucleoproteins / Q000172:deficiency / Q000502:physiology*; D006801:Humans; D038941:Polypyrimidine Tract-Binding Protein / Q000172:deficiency / Q000502:physiology*; D017448:Receptors, Dopamine D2 / Q000096:biosynthesis / Q000235:genetics*; D015854:Up-Regulation / Q000235:genetics
D065127:Dopamine D2 Receptor Antagonists; D034441:Heterogeneous-Nuclear Ribonucleoproteins; C450006:PTBP1 protein, human; D017448:Receptors, Dopamine D2; D038941:Polypyrimidine Tract-Binding Protein