Abstract
Reduced copy number of ribosomal protein (Rp) genes adversely affects both flies and mammals. Xrp1 encodes a reportedly Drosophila-specific AT-hook, bZIP protein responsible for many of the effects including the elimination of Rp mutant cells by competition with wild type cells. Irbp18, an evolutionarily conserved bZIP gene, heterodimerizes with Xrp1 and with another bZip protein, dATF4. We show that Irbp18 is required for the effects of Xrp1, whereas dATF4 does not share the same phenotype, indicating that Xrp1/Irbp18 is the complex active in Rp mutant cells, independently of other complexes that share Irbp18. Xrp1 and Irbp18 transcripts and proteins are upregulated in Rp mutant cells by auto-regulatory expression that depends on the Xrp1 DNA binding domains and is necessary for cell competition. We show that Xrp1 is conserved beyond Drosophila, although under positive selection for rapid evolution, and that at least one human bZip protein can similarly affect Drosophila development.
| Original language | English (US) |
|---|---|
| Article number | e50535 |
| Journal | eLife |
| Volume | 9 |
| DOIs | |
| State | Published - Jan 2020 |
Bibliographical note
Funding Information:We thank D Rio for antibodies, N Phadnis for advice, M Kiparaki and J Secombe for comments on the manuscript, J DiGregorio for discussions, J Chuen for technical assistance and C Smadja for Blast searches. This work was supported by grants from the NIH (EY026720 and GM120451 to NEB, and Developmental Biology Training Grant 5T32 HD0741 to JCC). Drosophila stocks were obtained from the Bloomington Drosophila Stock Center (supported by NIH P40OD018537). Confocal microscopy was performed in the Analytical Imaging Facility of the Albert Einstein College of Medicine (supported by the NCI P30CA013330) using Leica SP5 and SP8 microscopes, the latter acquired through NIH SIG 1S10 OD023591. DNA sequencing was performed by the Genomics Core of Albert Einstein College of Medicine.
Funding Information:
We thank D Rio for antibodies, N Phadnis for advice, M Kiparaki and J Secombe for comments on the manuscript, J DiGregorio for discussions, J Chuen for technical assistance and C Smadja for Blast searches. This work was supported by grants from the NIH (EY026720 and GM120451 to NEB, and Developmental Biology Training Grant 5T32 HD0741 to JCC). Drosophila stocks were obtained from the Bloomington Drosophila Stock Center (supported by NIH P40OD018537). Confocal microscopy was performed in the Analytical Imaging Facility of the Albert Einstein College of Medicine (supported by the NCI P30CA013330) using Leica SP5 and SP8 microscopes, the latter acquired through. National Eye Institute. EY026720. Nicholas E Baker. National Institute of General Medical Sciences. GM120451. Nicholas E Baker. Eunice Kennedy Shriver National Institute of Child Health and Human Development. 5T32 HD0741. Jacob C Cooper NIH SIG 1S10 OD023591. DNA sequencing was performed by the Genomics Core of Albert Einstein College of Medicine.
Publisher Copyright:
© Blanco et al.