ALKB-8 is a 2-oxoglutarate-dependent dioxygenase homologous to bacterial AlkB, which oxidatively demethylates DNA substrates. The mammalian AlkB family contains AlkB homologues denominated ALKBH1 to 8 and FTO. The C. elegans genome includes five AlkB-related genes, homologues of ALKBH1, 4, 6, 7, and 8, but lacks homologues of ALKBH2, 3, and 5 and FTO. ALKBH8 orthologues differ from other AlkB family members by possessing an additional methyltransferase module and an RNA binding N-terminal module. The ALKBH8 methyltransferase domain generates the wobble nucleoside 5-methoxycarbonylmethyluridine from its precursor 5-carboxymethyluridine and its (R)- and (S)-5-methoxycarbonylhydroxymethyluridine hydroxylated forms in tRNA Arg/UCG and tRNA Gly/UCC. The ALKBH8/ALKB-8 methyltransferase domain is highly similar to yeast TRM9, which selectively modulates translation of mRNAs enriched with AGA and GAA codons under both normal and stress conditions. In this report, we studied the role of alkb-8 in C. elegans. We show that downregulation of alkb-8 increases detection of lysosome-related organelles visualized by Nile red in vivo. Reversely, forced expression of alkb-8 strongly decreases the detection of this compartment. In addition, overexpression of alkb-8 applied in a pulse during the L1 larval stage increases the C. elegans lifespan.
- MeSH
- Caenorhabditis elegans embryologie enzymologie genetika MeSH
- dioxygenasy metabolismus MeSH
- dlouhověkost MeSH
- down regulace genetika MeSH
- embryo nesavčí metabolismus MeSH
- geneticky modifikovaná zvířata MeSH
- kyseliny ketoglutarové metabolismus MeSH
- larva metabolismus MeSH
- lyzozomy metabolismus MeSH
- methyltransferasy metabolismus MeSH
- operon MeSH
- promotorové oblasti (genetika) MeSH
- proteiny Caenorhabditis elegans genetika metabolismus MeSH
- RNA interference MeSH
- S-adenosylmethionin metabolismus MeSH
- stárnutí metabolismus MeSH
- vývojová regulace genové exprese MeSH
- zelené fluorescenční proteiny metabolismus MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
NHR-23, a conserved member of the nuclear receptor family of transcription factors, is required for normal development in Caenorhabditis elegans where it plays a critical role in growth and molting. In a search for NHR-23 dependent genes, we performed whole genome comparative expression microarrays on both control and nhr-23 inhibited synchronized larvae. Genes that decreased in response to nhr-23 RNAi included several collagen genes. Unexpectedly, several hedgehog-related genes were also down-regulated after nhr-23 RNAi. A homozygous nhr-23 deletion allele was used to confirm the RNAi knockdown phenotypes and the changes in gene expression. Our results indicate that NHR-23 is a critical co-regulator of functionally linked genes involved in growth and molting and reveal evolutionary parallels among the ecdysozoa.
- MeSH
- Caenorhabditis elegans genetika růst a vývoj MeSH
- delece genu MeSH
- molekulární sekvence - údaje MeSH
- proteiny Caenorhabditis elegans genetika fyziologie MeSH
- proteiny hedgehog metabolismus MeSH
- receptory cytoplazmatické a nukleární genetika fyziologie MeSH
- sekvence aminokyselin MeSH
- shazování tělního pokryvu genetika MeSH
- transkripční faktory genetika fyziologie MeSH
- vývojová regulace genové exprese MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Intramural MeSH
- Publikační typ
- abstrakt z konference MeSH