Biological significance of a universally conserved transcription mediator in metazoan developmental signaling pathways

Transcription mediators are known to be required for regulated transcription in yeast and higher eukaryotes. However, little is known about the specific roles of mediators in vivo during development. In this report, we have characterized the biological functions of the C. elegans gene med-6, which is the homolog of the yeast mediator med-6. We first identified a genetic mutation in the med-6 gene by comparing genetic and physical maps and determining the molecular lesion. Next, we demonstrated that med-6 plays an important role in metazoan development by regulating the transcription of genes in evolutionarily conserved signaling pathways. We showed that med-6 is involved in the transcription of genes of the Ras pathway by showing that med-6 RNAi suppressed phenotypes associated with gain-of-function alleles of let-23 and let-60, and enhanced those associated with a reduction-of-function allele of lin-3. We also found that med-6 is involved in male ray development, which is partly mediated by the Wnt pathway. As MED-6 is universally conserved, including in yeast, and the mediator-related proteins that function in vulval and male ray development are metazoan specific, our results suggest the role of med-6 as a point of convergence where signals transmitted through metazoan-specific mediator-related proteins meet. In addition, RNAi experiments in rde-1 background showed that maternal and zygotic med-6 activities have distinct roles in development.