biostudies-literatureSandler JECaltech Beckman Institute Functional Genomics CenterNIHNIGMS NIH HHS773-784.e6https://www.ebi.ac.uk/biostudies/studies/S-EPMC6506262biostudies-literatureUnknown47(6)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. InDevelopmental cellA Developmental Program Truncates Long Transcripts to Temporally Regulate Cell Signaling.PMC6506262R35 GM118146R35GM118146Dunipace LStathopoulos AStepanik VSandler JEIrizarry JAmrhein HfalseA Developmental Program Truncates Long Transcripts to Temporally Regulate Cell Signaling.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. In2018-01-01T00:00:00Z2018 Dec2026-05-01T10:35:35.501Z2020-10-29T11:22:22ZS-EPMC65062623056251510.1016/j.devcel.2018.11.019