BioProject

Vitamin B12 is an essential micronutrient that functions in two metabolic pathways: the canonical propionate breakdown pathway and the methionine/S-adenosylmethionine (Met/SAM) cycle. More...

Vitamin B12 is an essential micronutrient that functions in two metabolic pathways: the canonical propionate breakdown pathway and the methionine/S-adenosylmethionine (Met/SAM) cycle. In Caenorhabditis elegans, low vitamin B12, or genetic perturbation of the canonical propionate breakdown pathway results in propionate accumulation and the transcriptional activation of a propionate shunt pathway. This propionate-dependent mechanism requires nhr-10 and is referred to as “B12-mechanism-I”. Here, we report that vitamin B12 represses the expression of Met/SAM cycle genes by a propionate-independent mechanism we refer to as “B12-mechanism-II”. This mechanism is activated by perturbations in the Met/SAM cycle, genetically or due to low dietary vitamin B12. B12-mechanism-II requires nhr-114 to activate Met/SAM cycle gene expression, the vitamin B12 transporter, pmp-5, and adjust influx and efflux of the cycle by activating msra-1 and repressing cbs-1, respectively. Taken together, Met/SAM cycle activity is sensed and transcriptionally adjusted to be in a tight metabolic regime. Overall design: C. elegans RNA-sequencing of two experiments. All animals in both experiments contain Pacdh-1::GFP transgene. Experiment 1: wild type and nhr-114 deletion treated with nothing or 25 mM methionine and fed E. coli OP50 for 48 hours in biological duplicate. Experiment 2 - wild type, metr-1 deletion, and metr-1 point mutant containing a deletion in nhr-10 were all grown on 20 nM vitamin B12 and treated with either vector or nhr-114 RNAi for 48 hours in biological duplicate. Less...