Fragile XE-associated familial mental retardation protein 2 (FMR2) acts as a potent transcription activator

M. A. Hillman, J. Gecz

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

Expansion of the FRAXE CCG repeat to a full mutation is associated with methylation and transcriptional silencing of the FMR2 gene, and as a consequence, mild-to-borderline mental retardation. FMR2 is a member of a family of four proteins, AF4, LAF4, FMR2, and AF5q31. The proteins associated with this family localize to the cell nucleus. Various regions of FMR2, and each of the other members of the protein family, were cloned and analyzed for transcription activation in yeast and mammalian cells. In both yeast and mammalian cells, FMR2 showed strong transcription activation. AF4 activation potential was several-fold lower. Interestingly, isoforms of both FMR2 and LAF4 lacking exon 3 activated transcription better than the larger isoforms containing exon 3. Compared with the other members of the family, activation by FMR2 was the strongest. Our results show that FMR2 is a potent transcriptiof activator and that its function is conserved. Elucidation of the function of the FMR2 protein as a transcription activator may place FMR2 within the molecular signalling pathways involved in nonspecific X-linked mental retardation (MRX).

LanguageEnglish
Pages251-259
Number of pages9
JournalJournal of Human Genetics
Volume46
Issue number5
DOIs
Publication statusPublished - 17 May 2001
Externally publishedYes

Keywords

  • AF4
  • AF5q31
  • Alternative splicing
  • FMR2
  • LAF4
  • Transcription activation
  • XLMR

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

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title = "Fragile XE-associated familial mental retardation protein 2 (FMR2) acts as a potent transcription activator",
abstract = "Expansion of the FRAXE CCG repeat to a full mutation is associated with methylation and transcriptional silencing of the FMR2 gene, and as a consequence, mild-to-borderline mental retardation. FMR2 is a member of a family of four proteins, AF4, LAF4, FMR2, and AF5q31. The proteins associated with this family localize to the cell nucleus. Various regions of FMR2, and each of the other members of the protein family, were cloned and analyzed for transcription activation in yeast and mammalian cells. In both yeast and mammalian cells, FMR2 showed strong transcription activation. AF4 activation potential was several-fold lower. Interestingly, isoforms of both FMR2 and LAF4 lacking exon 3 activated transcription better than the larger isoforms containing exon 3. Compared with the other members of the family, activation by FMR2 was the strongest. Our results show that FMR2 is a potent transcriptiof activator and that its function is conserved. Elucidation of the function of the FMR2 protein as a transcription activator may place FMR2 within the molecular signalling pathways involved in nonspecific X-linked mental retardation (MRX).",
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Fragile XE-associated familial mental retardation protein 2 (FMR2) acts as a potent transcription activator. / Hillman, M. A.; Gecz, J.

In: Journal of Human Genetics, Vol. 46, No. 5, 17.05.2001, p. 251-259.

Research output: Contribution to journalArticle

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