In mammals, translational control plays critical roles during oocyte-to-embryo transition (OET) when transcription ceases. However, the underlying regulatory mechanisms remain challenging to study. Here, using low-input Ribo-seq (Ribo-lite), we investigated translational landscapes during OET using 30–150 mouse oocytes or embryos per stage. Ribo-lite can also accommodate single oocytes. Combining PAIso-seq to interrogate poly(A) tail lengths, we found a global switch of translatome that closely parallels changes of poly(A) tails upon meiotic resumption. Translation activation correlates with polyadenylation and is supported by polyadenylation signal proximal cytoplasmic polyadenylation elements (papCPEs) in 3′ untranslated regions. By contrast, translation repression parallels global de-adenylation. The latter includes transcripts containing no CPEs or non-papCPEs, which encode many transcription regulators that are preferentially re-activated before zygotic genome activation. CCR4-NOT, the major de-adenylation complex, and its key adaptor protein BTG4 regulate translation downregulation often independent of RNA decay. BTG4 is not essential for global de-adenylation but is required for selective gene de-adenylation and production of very short-tailed transcripts. In sum, our data reveal intimate interplays among translation, RNA stability and poly(A) tail length regulation underlying mammalian OET.

在哺乳动物中，当转录停止时，翻译控制在卵母细胞到胚胎的转变 (OET) 过程中起着关键作用。然而，潜在的监管机制仍然难以研究。在这里，我们使用低输入 Ribo-seq（Ribo-lite）研究了 OET 期间的平移景观，每个阶段使用 30-150 个小鼠卵母细胞或胚胎。Ribo-lite 也可以容纳单个卵母细胞。结合 PAIso-seq 来询问 poly(A) 尾长度，我们发现了一个翻译组的全局开关，它与减数分裂恢复时 poly(A) 尾的变化密切相关。翻译激活与聚腺苷酸化相关，并由 3' 非翻译区中的聚腺苷酸信号近端细胞质聚腺苷酸化元件 (papCPE) 支持。相比之下，翻译抑制与全局去腺苷酸化平行。后者包括不含 CPE 或非 papCPE 的转录本，它们编码许多在合子基因组激活之前优先重新激活的转录调节因子。CCR4-NOT 是主要的去腺苷酸化复合物，其关键衔接蛋白 BTG4 调节翻译下调，通常与 RNA 衰变无关。BTG4 对于全局去腺苷酸化不是必需的，但对于选择性基因去腺苷酸化和极短尾转录物的产生是必需的。总之，我们的数据揭示了哺乳动物 OET 背后的翻译、RNA 稳定性和 poly(A) 尾长调节之间的密切相互作用。及其关键衔接蛋白 BTG4 调节翻译下调通常独立于 RNA 衰变。BTG4 对于全局去腺苷酸化不是必需的，但对于选择性基因去腺苷酸化和极短尾转录物的产生是必需的。总之，我们的数据揭示了哺乳动物 OET 背后的翻译、RNA 稳定性和 poly(A) 尾长调节之间的密切相互作用。及其关键衔接蛋白 BTG4 调节翻译下调通常独立于 RNA 衰变。BTG4 对于全局去腺苷酸化不是必需的，但对于选择性基因去腺苷酸化和极短尾转录物的产生是必需的。总之，我们的数据揭示了哺乳动物 OET 背后的翻译、RNA 稳定性和 poly(A) 尾长调节之间的密切相互作用。