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The expression of HMGA1a is increased in lymphoblastoid cell lines from schizophrenia patients.

Abstract
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.
AuthorsTomomi Morikawa, Takayuki Manabe, Yoshihito Ito, Shinnosuke Yamada, Akira Yoshimi, Taku Nagai, Norio Ozaki, Akila Mayeda
JournalNeurochemistry international (Neurochem Int) 2010 May-Jun Vol. 56 Issue 6-7 Pg. 736-9 ISSN: 1872-9754 [Electronic] England
PMID20347905 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright 2010 Elsevier Ltd. All rights reserved.
Chemical References
  • RNA, Messenger
  • HMGA1b Protein
  • HMGA1a Protein
Topics
  • Alternative Splicing (genetics)
  • Cell Line, Transformed
  • Cell Nucleus (chemistry)
  • Gene Expression
  • HMGA1a Protein (analysis, genetics)
  • HMGA1b Protein (genetics)
  • Humans
  • Immunoblotting
  • Lymphocytes (chemistry, ultrastructure)
  • RNA, Messenger (analysis)
  • Reverse Transcriptase Polymerase Chain Reaction
  • Schizophrenia (genetics)
  • Up-Regulation

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