Center for Molecular Biology of Heidelberg University (ZMBH), DKFZ-ZMBH Alliance, Heidelberg, Germany.
Mol Microbiol. 2020 Feb;113(2):430-451. doi: 10.1111/mmi.14429. Epub 2019 Dec 11.
ZC3H20 and ZC3H21 are related trypanosome proteins with two C(x) C(x) C(x) 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.
ZC3H20 和 ZC3H21 是两种具有两个 C(x) C(x) C(x) H 锌指模体的相关锥虫蛋白。ZC3H20 在复制的哺乳动物感染性血淋巴形式中含量较低，但在高密度生长停滞时会变得更加丰富；ZC3H21 仅出现在寄生虫的前鞭毛体形式中，它感染采采蝇。每种蛋白质都结合了几百个 mRNA，具有重叠但不相同的特异性。两者都增加了结合的 mRNA 的表达，可能是通过招募 MKT1-PBP1 复合物。在 ZC3H20 耗尽或 ZC3H20 和 ZC3H21 同时耗尽后，至少有 28 个结合的 mRNA 减少；它们的产物包括质膜和能量代谢的前鞭毛体特异性蛋白。同时耗尽 ZC3H20 和 ZC3H21 会导致前鞭毛体缩小并停止生长；除了靶 mRNA 的减少之外，还有其他变化表明失去了发育调控。血淋巴形式特异性蛋白 RBP10 控制 ZC3H20 和 ZC3H21 的表达。有趣的是，一些 ZC3H20/21 靶 mRNA 也与 RBP10 结合并受到 RBP10 的抑制，允许在 RBP10 减少和 ZC3H20 和 ZC3H21 在分化过程中增加时进行动态调节。
