The juvenile-to-adult (J/A) transition of many animals, from worms to humans, is regulated by the highly conserved RNA-binding protein LIN-28. In this and other contexts – including stem cell renewal versus differentiation decisions – LIN-28 acts to suppress the production of the microRNA let-7, which in turn inhibits a suite of downstream genes, most notably the translational regulator LIN-41. Now, using the J/A transition of C. elegans as a model, David Fitch and colleagues () identify a new player in this axis, the Makorin orthologue LEP-2. lep-2 mutant adults display a number of juvenile characteristics, including failure of male tail tip retraction, continued moulting into adulthood and defective male sexual behaviour. The authors provide evidence that LEP-2 acts to promote degradation of LIN-28 in larval stages, which is necessary for the J/A transition. The underlying molecular mechanism has yet to be resolved: as a putative E3 ubiquitin ligase, LEP-2 might directly target LIN-28 for degradation or it may act indirectly. Given the conservation of the Makorin family, along with data implicating mammalian Makorins in cell state transitions and in the timing of puberty onset, it is possible that this Makorin/LIN-28 interaction could control developmental switches in multiple contexts.
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