RNA binding activity of Mkrn3 directs translation and cellular distribuition of the Gnrh1 precurser protein away from the the site of its processing to the mature GnRH peptide

Makorin Ring Finger Protein 3 (MKRN3) loss-of-function mutations are the most common genetic cause of central precocious puberty. Its hypothalamic mRNA levels drop leading up to puberty, and it appears to play a crucial repressive role in the central control of pubertal onset. MKRN3 has E3 ubquitin ligase and RNA binding domains, however, its actions in blocking puberty remain unclear, given the diverse actions and targets reported and observed in knockout models. To elucidate its role in GnRH neurons, we generated several high-throughput datasets to examine effects of Mkrn3 on various layers of regulation, including transcription, translation, RNA stability, protein stability, and RNA localization.