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The xbp-1 gene is essential for development in Drosophila

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We report in this paper the characterization of Dxbp-1, the Drosophila homologue of the xpb-1 gene that encodes a “bZIP”-containing transcription factor that plays a key role in the unfolded protein response (UPR), an evolutionarily conserved signalling pathway activated by an overload of misfolded proteins in the endoplasmic reticulum (ER). Dxbp-1 is ubiquitously transcribed, and high levels are found in embryonic salivary glands and in the ovarian follicle cells committed to the synthesis of the respiratory appendages. Loss of function of Dxbp-1 induced a recessive larval lethality, thus, revealing an essential requirement for this gene. The Dxbp-1 transcript was submitted to an “unconventional” splicing that generated a processed Dxbp-1s transcript encoding a DXbp-1 protein isoform, as is the case for yeast, Caenorhabditis elegans and vertebrate hac1/xbp-1 transcripts after UPR activation. However, in the absence of exogenously induced ER stress, the Dxbp-1s transcript was also detectable not only throughout embryonic and larval development but also in adults with a high level of accumulation in the male sexual apparatus and, to a lesser extent, in the salivary glands of the third-instar larvae. Using a Dxbp-1:GFP transgene as an in vivo reporter for Dxbp-1 mRNA unconventional splicing, we confirmed that Dxbp-1 processing took place in the salivary glands of the third-instar larvae. The Dxbp-1 gene appears, thus, to play an essential role during the development of Drosophila, hypothetically by stimulating the folding capacities of the ER in cells committed to intense secretory activities.

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We thank Jean Maurice Dura for kindly providing the lio-Gal4 driver line and all the members of the laboratory for helpful discussions throughout the course of this work. We also thank the two anonymous reviewers for their insightful comments and suggestions. S.S. was supported by a predoctoral fellowship from the Fondation pour la Recherche Médicale.

Author information

Correspondence to Constantin Yanicostas.

Additional information

Communicated by C. Desplan

Electronic supplementary material

Fig. S1

Deduced sequences of DXbp-1u and DXbp-1s proteins. Amino acids of the amino-terminal region shared by the two proteins are depicted in black. Within this region, the basic domain is underlined and the leucine residues constituting the “leucine zipper” are indicated in green. Residues of the carboxy-terminal specific domains of the DXbp-1u and DXbp-1s proteins are represented in blue and red, respectively (GIF 12 841 kb)

Fig. S2

Hypothetical structures of Ire-1 cleavage sites. Secondary structure of Ire-1 cleavage sites (red arrowheads) and adjacent sequences of D. melanogaster, C. elegans, Brachydanio rerio and Mus musculus xbp-1 transcripts, as deduced from visual and in silico examinations of xbp-1 sequences (GIF 6 767 kb)

Fig. S3

ER stress induces putative Ire-1-dependent processing of Dxbp-1 RNA. RT-PCR analysis of Dxbp-1s accumulation after the activation of the UPR pathway in adults. PCR amplifications were performed using genomic DNA (Gen) or reverse transcribed RNA extracted from non-treated adults (0) or from flies fed with 20, 40 or 60 μg/ml tunicamycine (GIF 32 523 kb)

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Souid, S., Lepesant, J. & Yanicostas, C. The xbp-1 gene is essential for development in Drosophila . Dev Genes Evol 217, 159–167 (2007). https://doi.org/10.1007/s00427-006-0124-1

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  • Drosophila, xbp-1
  • Unconventional splicing
  • UPR signalling
  • Secretion