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Polypyrimidine tract‐binding protein 1 regulates the alternative splicing of dopamine receptor D 2
Author(s) -
Sasabe Toshikazu,
Futai Eugene,
Ishiura Shoichi
Publication year - 2011
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2010.07086.x
Subject(s) - polypyrimidine tract binding protein , alternative splicing , rna splicing , biology , splicing factor , microbiology and biotechnology , rna binding protein , gene isoform , genetics , messenger rna , rna , gene
J. Neurochem. (2011) 116, 76–81. Abstract 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.