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A Developmental Program Truncates Long Transcripts to Temporally Regulate Cell Signaling

Sandler, Jeremy E. and Irizarry, Jihyun and Stepanik, Vincent and Dunipace, Leslie and Amrhein, Henry and Stathopoulos, Angelike (2018) A Developmental Program Truncates Long Transcripts to Temporally Regulate Cell Signaling. Developmental Cell, 47 (6). pp. 773-784. ISSN 1534-5807. http://resolver.caltech.edu/CaltechAUTHORS:20181218-081538450

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Abstract

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.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1016/j.devcel.2018.11.019DOIArticle
ORCID:
AuthorORCID
Stathopoulos, Angelike0000-0001-6597-2036
Additional Information:© 2018 Elsevier Inc. Received 19 May 2017, Revised 30 September 2018, Accepted 13 November 2018, Available online 17 December 2018. We thank B. Williams and I. Antoshechkin for library construction and sequencing support (Millard and Muriel Jacobs Genetics and Genomics Laboratory, Caltech); C. Mayr for advice in implementing the 3′ RNA-seq protocol; T. Koromila and J. McGehee for technical support; H. Ashe for sharing fly stocks; H. Araujo for providing antibodies; and T. Cline, H. Lipshitz, and D. Rio for helpful discussions. This study was supported by NIH grant R35GM118146 to A.S. and by the Caltech Beckman Institute Functional Genomics Center (H.A.). Author Contributions: J.E.S. and A.S. designed the experimental approach. J.E.S. performed RACE, in situ hybridizations, RNAi, qPCR, RNA-seq, and transgenic embryo experiments. J.I. established CRISPR fly stocks and performed antibody stainings. V.S. performed immunoprecipitations and western blots, and L.D. generated transgenic embryos and performed in situ hybridizations. J.E.S., L.D., and A.S. analyzed data, and H.A. performed computational analysis on RNA-seq data. J.E.S. and A.S. wrote the manuscript with contributions from J.I., V.S., L.D., and H.A. The authors declare no competing interests.
Funders:
Funding AgencyGrant Number
NIHR35GM118146
Caltech Beckman InstituteUNSPECIFIED
Subject Keywords:Drosophila melanogaster; gene expression; truncated transcripts; short nuclear cycles; cellularization; TGF-ß signaling; Sex-lethal; short-gastrulation; embryo; cell signaling
Record Number:CaltechAUTHORS:20181218-081538450
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:20181218-081538450
Official Citation:Jeremy E. Sandler, Jihyun Irizarry, Vincent Stepanik, Leslie Dunipace, Henry Amrhein, Angelike Stathopoulos, A Developmental Program Truncates Long Transcripts to Temporally Regulate Cell Signaling, Developmental Cell, Volume 47, Issue 6, 2018, Pages 773-784.e6, ISSN 1534-5807, https://doi.org/10.1016/j.devcel.2018.11.019. (http://www.sciencedirect.com/science/article/pii/S1534580718309754)
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:91881
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:18 Dec 2018 17:45
Last Modified:18 Dec 2018 17:45

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