MKRN3 is associated with protein ubiquitination, in which a ubiquitin moiety is attached to a protein, thus tagging it for movement to the proteasome, where it is degraded. Ubiquitination can also be an indicator for signal transduction, cell-cycle regulation, differentiation and morphogenesis, and other nonproteolytic fates. The precise mechanism by which the deletion of MKRN3 leads to the early reactivation of pulsatile GnRH secretion remains to be elucidated. We found increased levels of Mkrn3 mRNA at young ages in the arcuate nucleus of male and female mice, with a striking reduction in levels immediately before puberty and low levels in adulthood (Fig. 3). The arcuate nucleus is considered to play a key role in puberty control in mice,29 and the pattern of Mkrn3 mRNA expression correlates with an inhibitory effect on the initiation of puberty in these animals. These data are in agreement with the identification of a loss-of-function mutation in patients with central precocious puberty, corroborating the view that the mutation has an inhibitory effect on the secretion of GnRH. The initiation of puberty is thought to result from
