Mkrn3, or makorin ring finger protein 3, is an inhibitor of puberty initiation. It is a maternally imprinted gene located on chromosome 15q11.2-q13, and its loss-of-function mutations are the most common known genetic cause of central precocious puberty (CPP) [1,4,5]. MKRN3 is a member of the makorin family of ubiquitin ligases, and is involved in regulating the reproductive axis by influencing the release of gonadotropin-releasing hormone (GnRH) [1,4,5].

In mouse models, Mkrn3 deletion in hypothalamic neurons led to early puberty onset in female mice. It was found that Mkrn3 deletion increased the number of dendritic spines in the arcuate nucleus, and also affected the expression of genes controlling hypothalamic development and plasticity. MKRN3 was shown to interact with insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1), and also targeted neurokinin B (NKB). Additionally, MKRN3-mediated ubiquitination of Poly(A)-binding proteins (PABPs) was found to modulate the stability and translation of GNRH1 mRNA, controlling both transcriptional and post-transcriptional switches of puberty initiation [2,3].

In conclusion, Mkrn3 plays a crucial inhibitory role in puberty onset through regulating hypothalamic development and plasticity, and influencing related molecules. The study of Mkrn3 knockout mouse models has provided important insights into the mechanism of central precocious puberty, helping to understand the genetic basis of this disorder and potentially guiding future treatment strategies [1,2,3,4,5].