International Worm Meeting,
Homologues of the bacterial DNA/RNA repair enzymes AlkB are found in many metazoan species. There are nine mammalian AlkB homologues formed by the Fe(II) and 2-oxoglutarate dependent dioxygenases including AlkB1 to AlkB8 and an obesity and diabetes related protein FTO. In the C. elegans genome, six clear homologues of AlkB proteins are found by homology searches. AlkB8 is more complex then the other members of the AlkB family. Three distinct functional domains can be recognized in its structure. In addition to its AlkB like demethylase domain, it contains an RNA binding motif at the N-terminus, and an S-adenosyl methionine - dependent methyl transferase at the C-terminus. AlkB8 homologues were shown to be involved in methylation of Wobble base in several tRNAs but no phenotype was found in AlkB8 null mice. In this work, we show that C. elegans AlkB8 is expressed stably during all developmental stages. We show that inhibition of AlkB8 leads to enhanced metabolic rate and faster larval development compared to the control larvae. Keeping with a general metabolic function, the overexpression of AlkB8 from transgenes regulated by heat shock responsive promoters revert the effects observed by RNAi. Our results show that C. elegans is a suitable model for functional analysis of metabolic functions of AlkB8. Acknowledgements: The work was supported by the grant 0021620806 from the Ministry of Education, Youth and Sports of the Czech Republic.