GLD-4-Mediated Translational Activation Regulates the Size of the Proliferative Germ Cell Pool in the Adult C. elegans Germ Line

To avoid organ dysfunction as a consequence of tissue diminution or tumorous growth,a tight balance between cell proliferation and differentiation is maintained in metazoans. however,cell-intrinsic gene expression mechanisms controlling adult tissue homeostasis remain poorly understood. by focusing on the adult caenorhabditis elegans reproductive tissue,we show that translational activation of mrnas is a fundamental mechanism to maintain tissue homeostasis. our genetic experiments identified the trf4/5-type cytoplasmic poly(a) polymerase (cytopap) gld-4 and its enzymatic activator gls-1 to perform a dual role in regulating the size of the proliferative zone. consistent with a ubiquitous expression of gld-4 cytopap in proliferative germ cells,its genetic activity is required to maintain a robust proliferative adult germ cell pool,presumably by regulating many mrna targets encoding proliferation-promoting factors. based on translational reporters and endogenous protein expression analyses,we found that gld-4 activity promotes glp-1/notch receptor expression,an essential factor of continued germ cell proliferation. rna-protein interaction assays documented also a physical association of the gld-4/gls-1 cytopap complex with glp-1 mrna,and ribosomal fractionation studies established that gld-4 cytopap activity facilitates translational efficiency of glp-1 mrna. moreover,we found that in proliferative cells the differentiation-promoting factor,gld-2 cytopap,is translationally repressed by the stem cell factor and puf-type rna-binding protein,fbf. this suggests that cytopap-mediated translational activation of proliferation-promoting factors,paired with puf-mediated translational repression of differentiation factors,forms a translational control circuit that expands the proliferative germ cell pool. our additional genetic experiments uncovered that the gld-4/gls-1 cytopap complex promotes also differentiation,forming a redundant translational circuit with gld-2 cytopap and the translational repressor gld-1 to restrict proliferation. together with previous findings,our combined data reveals two interconnected translational activation/repression circuitries of broadly conserved rna regulators that maintain the balance between adult germ cell proliferation and differentiation. © 2014 millonigg et al.