A Developmental Program Truncates Long Transcripts to Temporally Regulate Cell Signaling

• Published in: Developmental cell 2018-12, Vol.47 (6), p.773-784.e6
• Main Authors: Sandler, Jeremy E., Irizarry, Jihyun, Stepanik, Vincent, Dunipace, Leslie, Amrhein, Henry, Stathopoulos, Angelike
• Format: Article
• Language: English
• Subjects: Animals; Cell Nucleus - metabolism; cell signaling; cellularization; Drosophila melanogaster; Drosophila melanogaster - genetics; Drosophila melanogaster - metabolism; Drosophila Proteins - metabolism; Drosophila Proteins - physiology; embryo; Embryo, Nonmammalian - metabolism; Embryonic Development - physiology; gene expression; Gene Expression Profiling - methods; Gene Expression Regulation, Developmental - physiology; Mitosis - physiology; Morphogenesis; Regulatory Elements, Transcriptional - physiology; RNA Isoforms - physiology; RNA-Binding Proteins - physiology; Sex-lethal; short nuclear cycles; short-gastrulation; Signal Transduction - genetics; Terminator Regions, Genetic - physiology; TGF-ß signaling; Transcription, Genetic - physiology; truncated transcripts
• ISSN: 1534-5807; 1878-1551
• DOI: 10.1016/j.devcel.2018.11.019

Rapid mitotic divisions and a fixed transcription rate limit the maximal length of transcripts in early Drosophila embryos. Previous studies suggested that transcription of long genes is initiated but aborted, as early nuclear divisions have short interphases. Here, we identify long genes that are expressed during short nuclear cycles as truncated transcripts. The RNA binding protein Sex-lethal physically associates with transcripts for these genes and is required to support early termination to specify shorter transcript isoforms in early embryos of both sexes. In addition, one truncated transcript for the gene short-gastrulation encodes a product in embryos that functionally relates to a previously characterized dominant-negative form, which maintains TGF-β signaling in the off-state. In summary, our results reveal a developmental program of short transcripts functioning to help temporally regulate Drosophila embryonic development, keeping cell signaling at early stages to a minimum in order to support its proper initiation at cellularization. •Long transcripts are truncated during short nuclear cycles in Drosophila embryos•The RNA-binding protein Sex-lethal binds to transcripts and controls their truncation•Short transcript products are functional in signaling pathways, affecting initiation•Global 3′ RNA-seq identifies additional truncated transcripts suggesting a program Sandler et al. identify a developmental program where long genes are expressed during short nuclear cycles in the early Drosophila embryo as truncated short transcripts to temporally control signaling and developmental progression. The RNA binding protein Sex-lethal directly promotes short transcript generation in embryos of both sexes.