TY - JOUR
T1 - The expression of HMGA1a is increased in lymphoblastoid cell lines from schizophrenia patients
AU - Morikawa, Tomomi
AU - Manabe, Takayuki
AU - Ito, Yoshihito
AU - Yamada, Shinnosuke
AU - Yoshimi, Akira
AU - Nagai, Taku
AU - Ozaki, Norio
AU - Mayeda, Akila
N1 - Funding Information:
T. Manabe and T. Morikawa were supported by a Grant-in-Aid for Scientific Research on Innovative Areas (RNA regulation: area no. 3001). T. Manabe was partially supported by a Grant-in-Aid for Young Scientists (B) from the Ministry of Education, Culture, Sports, Science and Technology of Japan, and a grant for the encouragement of research from the Takeda Science Foundation. This work was supported in part by research grants from the Ministry of Education, Culture, Sports, Science, and Technology of Japan , the Ministry of Health, Labor, and Welfare of Japan , MEXT ACADEMIC FRONTIER , and the Core Research for Evolutional Science and Technology (NO) .
PY - 2010/5
Y1 - 2010/5
N2 - The high-mobility group A protein 1a (HMGA1a) is a well-documented DNA-binding protein acting as an architectural transcription regulator. Recently, HMGA1a protein has been identified as a hypoxia-inducible RNA-binding trans-acting factor for aberrant splicing of presenilin-2 (PS2) pre-mRNA observed in the brains of sporadic Alzheimer's disease. Interestingly, this aberrant splicing of PS2 was also observed in the brains of bipolar disorder and schizophrenia. Many downstream genes under the control of HMGA1a could be associated with schizophrenia. On the other hand, many gene transcripts are aberrantly spliced in schizophrenia. Therefore, we examined the expression at the mRNA and protein levels of this DNA- and RNA-binding factor HMGA1a in the lymphoblastoid cell lines obtained from 16 schizophrenia patients with age-matched controls. We observed markedly higher HMGA1a mRNA and the increased HMGA1a protein in the nuclear fractions of schizophrenia patients. In contrast, there were no significant differences in the expression levels of HMGA1b, which is an alternatively spliced isoform of HMGA1a. The present study is the first to report a significant upregulation of HMGA1a in schizophrenia, suggesting its potential roles in both transcription and splicing of target genes linked with schizophrenia.
AB - The high-mobility group A protein 1a (HMGA1a) is a well-documented DNA-binding protein acting as an architectural transcription regulator. Recently, HMGA1a protein has been identified as a hypoxia-inducible RNA-binding trans-acting factor for aberrant splicing of presenilin-2 (PS2) pre-mRNA observed in the brains of sporadic Alzheimer's disease. Interestingly, this aberrant splicing of PS2 was also observed in the brains of bipolar disorder and schizophrenia. Many downstream genes under the control of HMGA1a could be associated with schizophrenia. On the other hand, many gene transcripts are aberrantly spliced in schizophrenia. Therefore, we examined the expression at the mRNA and protein levels of this DNA- and RNA-binding factor HMGA1a in the lymphoblastoid cell lines obtained from 16 schizophrenia patients with age-matched controls. We observed markedly higher HMGA1a mRNA and the increased HMGA1a protein in the nuclear fractions of schizophrenia patients. In contrast, there were no significant differences in the expression levels of HMGA1b, which is an alternatively spliced isoform of HMGA1a. The present study is the first to report a significant upregulation of HMGA1a in schizophrenia, suggesting its potential roles in both transcription and splicing of target genes linked with schizophrenia.
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U2 - 10.1016/j.neuint.2010.03.011
DO - 10.1016/j.neuint.2010.03.011
M3 - Article
C2 - 20347905
AN - SCOPUS:77952292585
SN - 0197-0186
VL - 56
SP - 736
EP - 739
JO - Neurochemistry International
JF - Neurochemistry International
IS - 6-7
ER -