Increased expression of splicing factor SRp20 mRNA in bipolar disorder patients.
BACKGROUND
Variations and defects in alternative splicing are well known to be associated with a variety of human diseases and the stress response. We previously reported a decrease in glucocorticoid receptor (GR) alpha, but not GRbeta in mood disorder patients, suggesting an aberrant alternative splicing mechanism. To examine whether altered RNA splicing may underlie the pathophysiology of mood disorder, we evaluated the expression of a variety of SR protein splicing factors, a family of proteins indispensable for proper alternative splicing, in mood disorder patients.


METHODS
We used quantitative real-time PCR to measure expressions of SRp20, SRp30c, SC35, SRp40, SRp46, SRp54, SRp55, SRp75, ASF/SF2, and 9G8 mRNA in peripheral white blood cells of 33 mood disorder patients during a depressive episode. In addition, the expressions of SRp20 and SC35 mRNA were quantified for 78 mood disorder patients in a remissive state, and 32 the first-degree relatives of these mood disorder patients.


RESULTS
A significant correlation was observed between SRp30c and the GRbeta/GRalpha ratio in control subjects, but not in mood disorder patients. Increased expression of SRp20 but not SRp30c mRNA was observed in bipolar disorder patients in both the depressive and remissive states. Major depressive disorder patients did not show any significant change in mRNA levels of SR proteins.


CONCLUSIONS
Subjects were Japanese adults. Patient treatment was not standardized.


CONCLUSIONS
These results suggest that aberrant alternative splicing machinery caused by increased SRp20 mRNA expression would be associated with the pathophysiology of bipolar disorder.
Watanuki
Toshio
T
Division of Neuropsychiatry, Department of Neuroscience, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-kogushi, Ube, Yamaguchi 755-8505, Japan.
Funato
Hiromasa
H
Uchida
Shusaku
S
Matsubara
Toshio
T
Kobayashi
Ayumi
A
Wakabayashi
Yusuke
Y
Otsuki
Koji
K
Nishida
Akira
A
Watanabe
Yoshifumi
Y
D017398:Alternative Splicing / Q000235:genetics* / Q000502:physiology; D001714:Bipolar Disorder / Q000235:genetics* / Q000503:physiopathology* / Q000523:psychology; D035061:Control Groups; D003865:Major Depressive Disorder / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D005190:Family / Q000523:psychology; D005260:Female; D015870:Gene Expression / Q000235:genetics; D006801:Humans; D007962:Leukocytes / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D012326:RNA Splicing / Q000235:genetics / Q000502:physiology; D020871:RNA Stability / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D011965:Receptors, Glucocorticoid / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000068103:Serine-Arginine Splicing Factors
D009687:Nuclear Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D011965:Receptors, Glucocorticoid; C491388:SRSF3 protein, human; C411470:glucocorticoid receptor alpha; C121943:glucocorticoid receptor beta; D000068103:Serine-Arginine Splicing Factors