Key result
Simultaneous depletion of ZC3H20 and ZC3H21 in Trypanosoma brucei causes procyclic forms to shrink and stop growing, accompanied by decreases in target mRNAs.
ZC3H20 and ZC3H21 are essential for the growth and developmental regulation of procyclic form Trypanosoma brucei by stabilizing specific mRNAs.
May inform antiparasitic strategies for trypanosomiasis; leaves open validation of ZC3H20/21 as therapeutic targets.
H zinc finger motifs. ZC3H20 is present at a low level in replicating mammalian-infective bloodstream forms, but becomes more abundant when they undergo growth arrest at high density; ZC3H21 appears only in the procyclic form of the parasite, which infects Tsetse flies. Each protein binds to several hundred mRNAs, with overlapping but not identical specificities. Both increase expression of bound mRNAs, probably through recruitment of the MKT1-PBP1 complex. At least 28 of the bound mRNAs decrease after depletion of ZC3H20, or of ZC3H20 and ZC3H21 together; their products include procyclic-specific proteins of the plasma membrane and energy metabolism. Simultaneous depletion of ZC3H20 and ZC3H21 causes procyclic forms to shrink and stop growing; in addition to decreases in target mRNAs, there are other changes suggestive of loss of developmental regulation. The bloodstream-form-specific protein RBP10 controls ZC3H20 and ZC3H21 expression. Interestingly, some ZC3H20/21 target mRNAs also bind to and are repressed by RBP10, allowing for dynamic regulation as RBP10 decreases and ZC3H20 and ZC3H21 increase during differentiation.
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Liu et al. (2019) studied Trypanosoma brucei. Depletion of ZC3H20 and ZC3H21 was evaluated on Parasite growth and mRNA expression. Simultaneous depletion of ZC3H20 and ZC3H21 in Trypanosoma brucei causes procyclic forms to shrink and stop growing, accompanied by decreases in target mRNAs.
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