title: 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.
authors.affiliation: Department of Basic Medical Sciences, University of Bari Aldo Moro, Bari, Italy. pndm01lf@uniba.it
authors.forename: Damiano
authors.initials: D
authors.lastname: Panelli
authors.forename: Francesca Paola
authors.initials: FP
authors.lastname: Lorusso
authors.forename: Francesco
authors.initials: F
authors.lastname: Papa
authors.forename: Patrizio
authors.initials: P
authors.lastname: Panelli
authors.forename: Alessandro
authors.initials: A
authors.lastname: Stella
authors.forename: Massimo
authors.initials: M
authors.lastname: Caputi
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Sardanelli
authors.forename: Sergio
authors.initials: S
authors.lastname: Papa
mesh_terms: D017398:Alternative Splicing / Q000235:genetics*; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D042967:Electron Transport Complex I / Q000235:genetics / Q000378:metabolism; D005091:Exons; D005786:Gene Expression Regulation; D050172:Genes, X-Linked; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D009447:Neuroblastoma / Q000235:genetics / Q000378:metabolism; D020033:Protein Isoforms / Q000235:genetics; D012402:Rotenone / Q000494:pharmacology
chemical_list: C518653:NDUFB11 protein, human; D020033:Protein Isoforms; D012402:Rotenone; D042967:Electron Transport Complex I