GEI-8, a Homologue of Vertebrate Nuclear Receptor Corepressor NCoR/SMRT, Regulates Gonad Development and Neuronal Functions in Caenorhabditis elegans

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung

Beitragende

  • Pavol Mikoláš - , Karlsuniversität Prag (Autor:in)
  • Johana Kollárová - , Karlsuniversität Prag (Autor:in)
  • Kateřina Šebková - , Karlsuniversität Prag (Autor:in)
  • Vladimír Saudek - , Karlsuniversität Prag (Autor:in)
  • Petr Yilma - , Karlsuniversität Prag (Autor:in)
  • Markéta Kostrouchová - , Karlsuniversität Prag (Autor:in)
  • Michael W. Krause - , National Institutes of Health (NIH) (Autor:in)
  • Zdenek Kostrouch - , Karlsuniversität Prag (Autor:in)
  • Marta Kostrouchová - , Karlsuniversität Prag (Autor:in)

Abstract

NCoR and SMRT are two paralogous vertebrate proteins that function as corepressors with unliganded nuclear receptors. Although C. elegans has a large number of nuclear receptors, orthologues of the corepressors NCoR and SMRT have not unambiguously been identified in Drosophila or C. elegans. Here, we identify GEI-8 as the closest homologue of NCoR and SMRT in C. elegans and demonstrate that GEI-8 is expressed as at least two isoforms throughout development in multiple tissues, including neurons, muscle and intestinal cells. We demonstrate that a homozygous deletion within the gei-8 coding region, which is predicted to encode a truncated protein lacking the predicted NR domain, results in severe mutant phenotypes with developmental defects, slow movement and growth, arrested gonadogenesis and defects in cholinergic neurotransmission. Whole genome expression analysis by microarrays identified sets of de-regulated genes consistent with both the observed mutant phenotypes and a role of GEI-8 in regulating transcription. Interestingly, the upregulated transcripts included a predicted mitochondrial sulfide:quinine reductase encoded by Y9C9A.16. This locus also contains non-coding, 21-U RNAs of the piRNA class. Inhibition of the expression of the region coding for 21-U RNAs leads to irregular gonadogenesis in the homozygous gei-8 mutants, but not in an otherwise wild-type background, suggesting that GEI-8 may function in concert with the 21-U RNAs to regulate gonadogenesis. Our results confirm that GEI-8 is the orthologue of the vertebrate NCoR/SMRT corepressors and demonstrate important roles for this putative transcriptional corepressor in development and neuronal function.

Details

OriginalspracheEnglisch
Aufsatznummere58462
FachzeitschriftPloS one
Jahrgang8
Ausgabenummer3
PublikationsstatusVeröffentlicht - 6 März 2013
Peer-Review-StatusJa
Extern publiziertJa

Externe IDs

PubMed PMC3590189
Scopus 84874605154
PubMed 23484030

Schlagworte