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

Transcription mediators are known to be required for regulated transcriptio n in yeast and higher eukaryotes. However, little is known about the specif ic roles of mediators in vivo during development. In this report, we have c haracterized 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 mut ation in the med-6 gene by comparing genetic and physical maps and determin ing the molecular lesion. Next, we demonstrated that med-6 plays an importa nt role in metazoan development by regulating the transcription of genes in evolutionarily conserved signaling pathways. We showed that med-6 is invol ved 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 a llele of lin-3. We also found that med-6 is involved in male ray developmen t, which is partly mediated by the Wnt pathway. As MED-6 is universally con served, including in yeast, and the mediator-related proteins that function in vulval and male ray development are metazoan specific, our results sugg est the role of med-6 as a point of convergence where signals transmitted t hrough metazoan-specific mediator-related proteins meet. In addition, RNAi experiments in rde-1 background showed that maternal and zygotic med-6 acti vities have distinct roles in development.