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The mechanism of alternative splicing of the X-linked NDUFB11 gene of the respiratory chain complex I, impact of rotenone treatment in neuroblastoma cells.

Abstract
A study is presented on the regulation of alternative splicing (AS) of the Ndufb11 gene of complex I of the mitochondrial respiratory chain and the impact on this process of rotenone treatment in neuroblastoma cells. In physiological conditions the Ndufb11 gene produces at high level a short transcript isoform encoding for a 153 aa protein. This subunit is essential for the assembly of a functional and stable mammalian complex I. The gene produces also, at low level, a longer transcript isoform encoding for a 163 aa protein whose role is unknown. Evidence is presented here showing that the level of the two isoforms is regulated by three DGGGD ESS elements located in exon 2 which can bind the hnRNPH1 protein. In neuronal cells rotenone treatment affects the Ndufb11 alternative splicing pathway, with the increase of the 163/153 mRNAs ratio. This effect appears to be due to the down-regulation of the hnRNPH1 protein. Since rotenone induces apoptosis in neuronal cells, the post-transcriptional regulation of the Ndufb11 gene can be involved in the programmed cell death process.
AuthorsDamiano Panelli, Francesca Paola Lorusso, Francesco Papa, Patrizio Panelli, Alessandro Stella, Massimo Caputi, Anna Maria Sardanelli, Sergio Papa
JournalBiochimica et biophysica acta (Biochim Biophys Acta) Vol. 1829 Issue 2 Pg. 211-8 (Feb 2013) ISSN: 0006-3002 [Print] Netherlands
PMID23246602 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2012 Elsevier B.V. All rights reserved.
Chemical References
  • NDUFB11 protein, human
  • Protein Isoforms
  • Rotenone
  • Electron Transport Complex I
Topics
  • Alternative Splicing (genetics)
  • Apoptosis (drug effects, genetics)
  • Cell Line, Tumor
  • Electron Transport Complex I (genetics, metabolism)
  • Exons
  • Gene Expression Regulation
  • Genes, X-Linked
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • Neuroblastoma (genetics, metabolism)
  • Protein Isoforms (genetics)
  • Rotenone (pharmacology)

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