Dopamine and glutamate induce distinct striatal splice forms of Ania-6, an RNA polymerase II-associated cyclin.
Control of neuronal gene expression by drugs or neurotransmitters is a critical step in long-term neural plasticity. Here, we show that a gene induced in the striatum by cocaine or direct dopamine stimulation, ania-6, is a member of a novel family of cyclins with homology to cyclins K/T/H/C. Further, different types of neurotransmitter stimulation cause selective induction of distinct ania-6 isoforms, through alternative splicing. The longer Ania-6 protein colocalizes with nuclear speckles and is associated with key elements of the RNA elongation/processing complex, including the hyperphosphorylated form of RNA polymerase II, the splicing factor SC-35, and the p110 PITSLRE cyclin-dependent kinase. Distinct types of neuronal stimulation may therefore differentially modulate nuclear RNA processing, through altered transcription and splicing of ania-6.
Berke
J D
JD
Molecular Plasticity Section, National Institute of Neurological Disorders and Stroke, Bethesda, MD 20892, USA.
Sgambato
V
V
Zhu
P P
PP
Lavoie
B
B
Vincent
M
M
Krause
M
M
Hyman
S E
SE
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D003042:Cocaine / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D016213:Cyclins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D004298:Dopamine / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D017781:Genes, Immediate-Early; D018698:Glutamic Acid / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D016716:PC12 Cells; D010300:Parkinson Disease / Q000378:metabolism; D010766:Phosphorylation; D012319:RNA Polymerase II / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014162:Transfection
C439931:Ccnl1 protein, mouse; C499077:Ccnl1 protein, rat; C499078:Ccnl2 protein, mouse; D016213:Cyclins; D018698:Glutamic Acid; D018844:Cyclin-Dependent Kinases; D012319:RNA Polymerase II; D003042:Cocaine; D004298:Dopamine