Boymaw, overexpressed in brains with major psychiatric disorders, may encode a small protein to inhibit mitochondrial function and protein translation

Am J Med Genet B Neuropsychiatr Genet. 2015 Jun;168B(4):284-95. doi: 10.1002/ajmg.b.32311. Epub 2015 May 5.

Abstract

The t(1,11) chromosome translocation co-segregates with major psychiatric disorders in a large Scottish family. The translocation disrupts the DISC1and Boymaw (DISC1FP1) genes on chromosomes 1 and 11, respectively. After translocation, two fusion genes are generated. Our recent studies found that the DISC1-Boymaw fusion protein is localized in mitochondria and inhibits oxidoreductase activity, rRNA expression, and protein translation. Mice carrying the DISC1-Boymaw fusion genes display intermediate behavioral phenotypes related to major psychiatric disorders. Here, we report that the Boymaw gene may encode a small protein predominantly localized in mitochondria. The Boymaw protein inhibits oxidoreductase activity, rRNA expression, and protein translation in the same way as the DISC1-Boymaw fusion protein. Interestingly, Boymaw expression is up-regulated by different stressors at RNA and/or protein translational levels. In addition, we found that Boymaw RNA expression is significantly increased in the postmortem brains of patients with major psychiatric disorders. Our studies therefore suggest that the Boymaw gene could potentially be a susceptibility gene for major psychiatric disorders in both the Scottish t(1,11) family and the general population of patients.

Keywords: boymaw; mitochondria; oxidoreductase; protein translation; psychiatric disorder; stress.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Brain / metabolism*
  • Brain / pathology
  • COS Cells
  • Chlorocebus aethiops
  • HEK293 Cells
  • Humans
  • Mental Disorders / metabolism*
  • Mitochondria / metabolism*
  • Molecular Sequence Data
  • Open Reading Frames / genetics
  • Postmortem Changes
  • Protein Biosynthesis*
  • Protein Transport
  • RNA, Long Noncoding
  • RNA, Ribosomal / metabolism
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism*
  • Stress, Physiological / genetics

Substances

  • DISC1FP1 non-coding RNA, human
  • RNA, Long Noncoding
  • RNA, Ribosomal
  • Recombinant Fusion Proteins