Pérez-Roldán Juan, Henn László, Bernués Jordi, Torras-LLort Mònica, Tamirisa Srividya, Belloc Eulàlia, Rodríguez-Muñoz Laura, Timinszky Gyula, Jiménez Gerardo, Méndez Raúl, Carbonell Albert, Azorín Fernando
Institute of Molecular Biology of Barcelona, CSIC, Baldiri Reixac, 4, 08028 Barcelona, Spain.
Institute for Research in Biomedicine, IRB Barcelona, The Barcelona Institute of Science and Technology, Baldiri Reixac, 10, 08028 Barcelona. Spain.
Nucleic Acids Res. 2025 Apr 10;53(7). doi: 10.1093/nar/gkaf288.
During early embryogenesis the zygotic genome remains transcriptionally silent and expression relies on maternally deposited products. Maternal deposition of histones is crucial to preserve chromatin integrity during early embryo development, when the number of nuclei exponentially increases in the absence of zygotic expression. In the Drosophila embryo, histones are maternally deposited as both proteins and mRNAs. Histone transcripts are the only nonpolyadenylated cellular mRNAs. They contain a highly conserved 3'UTR stem-loop structure, which is recognized by the Stem-Loop Binding Protein (SLBP) that, in conjunction with U7 snRNP, regulates their unique 3'-end processing. Here we report that, unexpectedly, maternal histone mRNAs are polyadenylated and have a truncated 3' stem-loop. This noncanonical 3'-end processing of maternal histone mRNAs occurs at their synthesis during oogenesis and requires SLBP, but not U7 snRNP. We show that maternal histone transcripts are subjected to cytoplasmic poly(A) tail elongation by Wisp, which results in their stabilization and is a requisite for translation. We also show that maternal histone transcripts remain largely quiescent and that their translation is activated upon loss of the embryonic linker histone dBigH1, which impairs chromatin assembly and induces DNA damage. Here, we discuss possible models to integrate these observations.
在早期胚胎发生过程中，合子基因组保持转录沉默，其表达依赖于母体沉积的产物。在早期胚胎发育过程中，当合子表达缺失而细胞核数量呈指数增加时，母体组蛋白的沉积对于维持染色质完整性至关重要。在果蝇胚胎中，组蛋白以蛋白质和mRNA的形式由母体沉积。组蛋白转录本是唯一非多聚腺苷酸化的细胞mRNA。它们含有一个高度保守的3'UTR茎环结构，该结构被茎环结合蛋白（SLBP）识别，SLBP与U7 snRNP一起调节其独特的3'端加工。在此我们报告，出乎意料的是，母体组蛋白mRNA被多聚腺苷酸化且具有截短的3'茎环。母体组蛋白mRNA的这种非经典3'端加工发生在卵子发生过程中它们的合成阶段，并且需要SLBP，但不需要U7 snRNP。我们表明，母体组蛋白转录本通过Wisp进行细胞质多聚（A）尾延伸，这导致它们的稳定并且是翻译所必需的。我们还表明，母体组蛋白转录本在很大程度上保持静止，并且它们的翻译在胚胎连接组蛋白dBigH1缺失时被激活，这会损害染色质组装并诱导DNA损伤。在此，我们讨论整合这些观察结果的可能模型。
