Primordial germ cells (PGCs) form during early embryogenesis with a supply of maternal mRNAs that contain shorter poly(A) tails. How translation of maternal mRNAs is regulated during PGC development remains elusive. Here we describe a small-molecule screen with zebrafish embryos that identified primordazine, a compound that selectively ablates PGCs. Primordazine's effect on PGCs arises from translation repression through primordazine-response elements in the 3′ UTRs. Systematic dissection of primordazine's mechanism of action revealed that translation of mRNAs during early embryogenesis occurs by two distinct pathways, depending on the length of their poly(A) tails. In addition to poly(A)-tail-dependent translation (PAT), early embryos perform poly(A)-tail-independent noncanonical translation (PAINT) via deadenylated 3′ UTRs. Primordazine inhibits PAINT without inhibiting PAT, an effect that was also observed in quiescent, but not proliferating, mammalian cells. These studies reveal that PAINT is an alternative form of translation in the early embryo and is indispensable for PGC maintenance.

原始生殖细胞（PGC）在早期胚胎形成过程中形成，并提供了包含较短poly（A）尾巴的母体mRNA。在PGC发育过程中如何调节母体mRNA的翻译仍不清楚。在这里，我们描述了一个带有斑马鱼胚胎的小分子屏幕，该屏幕识别了primordazine（一种选择性消融PGC的化合物）。primordazine对PGC的作用源于3'UTRs中通过primordazine响应元件进行的翻译抑制。系统性地剖析了primordazine的作用机理，发现早期胚胎发生过程中mRNA的翻译通过两种不同的途径发生，具体取决于它们的poly（A）尾巴的长度。除poly（A）-tail-dependent翻译（PAT）外，早期胚胎还通过腺苷酸化的3'UTRs进行poly（A）-tail-dependent非经典翻译（PAINT）。Primordazine抑制PAINT而又不抑制PAT，这种作用在静止但不增殖的哺乳动物细胞中也观察到。这些研究表明，PAINT是早期胚胎中的另一种翻译形式，对于PGC的维持是必不可少的。