Vitamin A deficiency affects gene expression in the Drosophila melanogaster head

Abstract

Insufficient dietary intake of vitamin A causes various human diseases. For instance, chronic vitamin A deprivation causes blindness, slow growth, impaired immunity, and an increased risk of mortality in children. In contrast to these diverse effects of vitamin A deficiency in mammals, chronic vitamin A deficiency in flies neither causes obvious developmental defects nor lethality. As in mammals, vitamin A deficiency in flies severely affects the visual system: it impairs the synthesis of the retinal chromophore, disrupts the formation of the visual pigments (Rhodopsins), and damages the photoreceptors. However, the molecular mechanisms that respond to vitamin A deficiency remain poorly understood. To identify genes and signaling pathways that are affected by vitamin A deficiency, we performed RNA-sequencing and differential gene expression analysis in Drosophila melanogaster. We found an upregulation of genes that are essential for the synthesis of the retinal chromophore, specific aminoacyl-tRNA synthetases, and major nutrient reservoir proteins. We also discovered that vitamin A deficiency affects several genes that are required for the termination of the light response: for instance, we found a downregulation of both arrestin genes that are essential for the inactivation of Rhodopsin. A comparison of the vitamin A deficiency-responsive genes with previously identified blue light stress-responsive genes revealed that the two types of environmental stress trigger largely nonoverlapping transcriptome responses. Yet, both stresses increase the expression of seven genes with poorly understood functions. Taken together, our transcriptome analysis offers insights into the molecular mechanisms that respond to environmental stresses.

Vitamin A Deficiency Alters the Phototransduction Machinery and Distinct Non-Vision-Specific Pathways in the Drosophila Eye Proteome

“…We discovered that vitamin A is not only required for the expression of the visual pigment Rh1, but also for most downstream phototransduction proteins ( Figure 5 B). Our previous [ 2 ] and current data suggest that their regulation involves vitamin A-dependent transcriptional as well as post-transcriptional mechanisms. A feedback mechanism decreases the expression of both arrestin genes in response to vitamin A deficiency [ 2 ] and we showed in the current study that this is consistent with the reduced protein levels of both visual Arrestins Arr1 and Arr2.…”

“…Our previous [ 2 ] and current data suggest that their regulation involves vitamin A-dependent transcriptional as well as post-transcriptional mechanisms. A feedback mechanism decreases the expression of both arrestin genes in response to vitamin A deficiency [ 2 ] and we showed in the current study that this is consistent with the reduced protein levels of both visual Arrestins Arr1 and Arr2. The Arr1 and Arr2 levels could be additionally reduced by translation inhibition through the PERK-eIF2 pathway in response to impaired maturation of Rh1 (see below).…”

“…The second regulatory mechanism that underlies the about 2-fold decrease in molar abundances of the other phototransduction components ( Figure 5 B) appears to be post-transcriptional, since the transcription of the respective genes is not vitamin A-dependent [ 2 ]. While the decrease of inhibitory Arrestins upon impaired visual signaling due to low Rh1 levels appears intuitive, the reduction of phototransduction proteins that transduce and amplify the visual signal (e.g., Galphaq, NorpA; Figure 5 B) or maintain the PI cycle is unexpected, since their decrease should additionally impair the speed and sensitivity of the visual response.…”

“…Our head transcriptome [ 2 ] and eye proteome analysis (this study) revealed that there are Drosophila genes and proteins that strongly respond to vitamin A deficiency but are not part of the visual signaling cascade. For instance, vitamin A deprivation altered components of the translation machinery, which would be consistent with translation inhibition as the result of an unfolded protein response [ 75 ] elicited by impaired Rh1 maturation in photoreceptor neurons.…”

“…Vitamin A is an essential nutrient that is required in vertebrates and invertebrates for the synthesis of the retinylidene chromophore and the visual pigments [ 1 , 2 , 3 , 4 ]. Like mammals, Drosophila cannot synthesize vitamin A de novo; both the lack of dietary vitamin A sources [ 5 , 6 , 7 ] and the mutation of genes that are required for vitamin A synthesis [ 8 , 9 ] cause severe visual defects.…”