Transcriptome profiling of aging Drosophila photoreceptors reveals gene expression trends that correlate with visual senescence

BackgroundAging is associated with functional decline of neurons and increased incidence of both neurodegenerative and ocular disease. Photoreceptor neurons in Drosophila melanogaster provide a powerful model for studying the molecular changes involved in functional senescence of neurons since decreased visual behavior precedes retinal degeneration. Here, we sought to identify gene expression changes and the genomic features of differentially regulated genes in photoreceptors that contribute to visual senescence.ResultsTo identify gene expression changes that could lead to visual senescence, we characterized the aging transcriptome of Drosophila sensory neurons highly enriched for photoreceptors. We profiled the nuclear transcriptome of genetically-labeled photoreceptors over a 40 day time course and identified increased expression of genes involved in stress and DNA damage response, and decreased expression of genes required for neuronal function. We further show that combinations of promoter motifs robustly identify age-regulated genes, suggesting that transcription factors are important in driving expression changes in aging photoreceptors. However, long, highly expressed and heavily spliced genes are also more likely to be downregulated with age, indicating that other mechanisms could contribute to expression changes at these genes. Lastly, we identify that circular RNAs (circRNAs) strongly increase during aging in photoreceptors.ConclusionsOverall, we identified changes in gene expression in aging Drosophila photoreceptors that could account for visual senescence. Further, we show that genomic features predict these age-related changes, suggesting potential mechanisms that could be targeted to slow the rate of age-associated visual decline.

• Publication year

  2017

• Venue

  BMC Genomics

• Publication date

  2017-11-21

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1186/s12864-017-4304-3PMID 29162050PMCID 5698953
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Circular RNA identification based on multiple seed matching

  2018cited by this paper
• Circadian deep sequencing reveals stress-response genes that adopt robust rhythmic expression during aging

  2017influential reference
• Transcriptional Signatures of Aging.

  2017influential reference
• Retinal gene expression responses to aging are sexually divergent

  2017cited by this paper
• Aging and Vision.

  2016cited by this paper
• Diet restriction delays accelerated aging and genomic stress in DNA repair deficient mice

  2016cited by this paper
• CircRNA accumulation in the aging mouse brain

  2016cited by this paper
• Auditory system of fruit flies.

  2016cited by this paper
• Genetic architecture of natural variation in visual senescence in Drosophila

  2016influential reference
• ER chaperones in neurodegenerative disease: Folding and beyond.

  2016cited by this paper
• Chromatin-modifying genetic interventions suppress age-associated transposable element activation and extend life span in Drosophila

  2016influential reference
• Transcriptome Profiling Identifies Multiplexin as a Target of SAGA Deubiquitinase Activity in Glia Required for Precise Axon Guidance During Drosophila Visual Development

  2016cited by this paper
• The crystal structure of human GlnRS provides basis for the development of neurological disorders

  2016cited by this paper
• A survey of best practices for RNA-seq data analysis

  2016cited by this paper
• Dynamics in Transcriptomics: Advancements in RNA-seq Time Course and Downstream Analysis

  2015cited by this paper
• Ca-α1T, a fly T-type Ca2+ channel, negatively modulates sleep

  2015cited by this paper
• Vision from next generation sequencing: multi-dimensional genome-wide analysis for producing gene regulatory networks underlying retinal development, aging and disease.

  2015cited by this paper
• CIRI: an efficient and unbiased algorithm for de novo circular RNA identification

  2015cited by this paper
• A decision underlies phototaxis in an insect

  2015cited by this paper
• Conservation of transcription factor binding specificities across 600 million years of bilateria evolution

  2015cited by this paper
• Disruption of DNA methylation-dependent long gene repression in Rett syndrome

  2015cited by this paper
• Mutations in Four Glycosyl Hydrolases Reveal a Highly Coordinated Pathway for Rhodopsin Biosynthesis and N-Glycan Trimming in Drosophila melanogaster

  2014cited by this paper
• Mouse strain and brain region‐specific expression of the glutaminyl cyclases QC and isoQC

  2014cited by this paper
• Affinity-based isolation of tagged nuclei from Drosophila tissues for gene expression analysis.

  2014cited by this paper
• RACK1 controls IRES-mediated translation of viruses.

  2014cited by this paper
• Alternative splicing in Drosophila neuronal development

  2014cited by this paper
• Cell type–specific mRNA purification by translating ribosome affinity purification (TRAP)

  2014cited by this paper
• GeneMANIA: Fast gene network construction and function prediction for Cytoscape

  2014cited by this paper
• circRNA biogenesis competes with pre-mRNA splicing.

  2014cited by this paper
• Next maSigPro: updating maSigPro bioconductor package for RNA-seq time series

  2014cited by this paper
• Genome-wide analysis of drosophila circular RNAs reveals their structural and sequence properties and age-dependent neural accumulation.

  2014influential reference
• featureCounts: an efficient general purpose program for assigning sequence reads to genomic features

  2013cited by this paper
• mTOR is a key modulator of ageing and age-related disease

  2013cited by this paper
• Topoisomerases facilitate transcription of long genes linked to autism

  2013cited by this paper
• The prevalence of age-related eye diseases and visual impairment in aging: current estimates.

  2013cited by this paper
• Cell-type-specific nuclei purification from whole animals for genome-wide expression and chromatin profiling.

  2012cited by this paper
• Potassium Channels in Drosophila: Historical Breakthroughs, Significance, and Perspectives

  2012cited by this paper
• Aging of human short-wave cone pathways

  2012cited by this paper
• Competition between Replicative and Translesion Polymerases during Homologous Recombination Repair in Drosophila

  2012cited by this paper
• Compartmentalization and Ca2+ Buffering Are Essential for Prevention of Light-Induced Retinal Degeneration

  2012cited by this paper
• Drosophila visual transduction.

  2012cited by this paper
• A role for small RNAs in DNA double-strand break repair.

  2012cited by this paper
• Diet and Energy-Sensing Inputs Affect TorC1-Mediated Axon Misrouting but Not TorC2-Directed Synapse Growth in a Drosophila Model of Tuberous Sclerosis

  2012cited by this paper
• Drosophila auditory organ genes and genetic hearing defects.

  2012cited by this paper
• The retinal mosaics of opsin expression in invertebrates and vertebrates

  2011cited by this paper
• Aging and vision.

  2011cited by this paper
• Age-Related Alterations in Neurons of the Mouse Retina

  2011cited by this paper
• The COMPASS Family of H3K4 Methylases in Drosophila

  2011cited by this paper
• NFAT regulates pre-synaptic development and activity-dependent plasticity in Drosophila.

  2011cited by this paper
• Controlling gene expression in response to stress

  2011cited by this paper
• pROC: an open-source package for R and S+ to analyze and compare ROC curves

  2011cited by this paper
• Differential changes in retina function with normal aging in humans

  2011cited by this paper
• Behavioral and Synaptic Plasticity Are Impaired upon Lack of the Synaptic Protein SAP47

  2011cited by this paper
• Simple combinations of lineage-determining transcription factors prime cis-regulatory elements required for macrophage and B cell identities.

  2010influential reference
• Dual Roles for DNA Polymerase Theta in Alternative End-Joining Repair of Double-Strand Breaks in Drosophila

  2010cited by this paper
• Photoreceptor degeneration: genetic and mechanistic dissection of a complex trait

  2010cited by this paper
• Neural mechanisms of ageing and cognitive decline

  2010cited by this paper
• Age-Related Deterioration of Rod Vision in Mice

  2010cited by this paper
• Distinct Signature of Altered Homeostasis in Aging Rod Photoreceptors: Implications for Retinal Diseases

  2010cited by this paper
• The MIQE guidelines: minimum information for publication of quantitative real-time PCR experiments.

  2009cited by this paper
• Temporal patterns of broad isoform expression during the development of neuronal lineages in Drosophila

  2009cited by this paper
• edgeR: a Bioconductor package for differential expression analysis of digital gene expression data

  2009cited by this paper
• Long-lived Indy induces reduced mitochondrial reactive oxygen species production and oxidative damage

  2009cited by this paper
• DAP5 promotes cap-independent translation of Bcl-2 and CDK1 to facilitate cell survival during mitosis.

  2008cited by this paper
• Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources

  2008cited by this paper
• Evolution of the Aging Brain Transcriptome and Synaptic Regulation

  2008cited by this paper
• Application of a translational profiling approach for the comparative analysis of CNS cell types.

  2008cited by this paper
• An RNA interference screen identifies a novel regulator of target of rapamycin that mediates hypoxia suppression of translation in Drosophila S2 cells.

  2008cited by this paper
• Gene expression changes in the course of normal brain aging are sexually dimorphic

  2008cited by this paper
• Queuine promotes antioxidant defence system by activating cellular antioxidant enzyme activities in cancer.

  2008cited by this paper
• Prolonged Gq activity triggers fly rhodopsin endocytosis and degradation, and reduces photoreceptor sensitivity

  2007cited by this paper
• Foxo and Fos regulate the decision between cell death and survival in response to UV irradiation

  2007cited by this paper
• Unfolded protein response in a Drosophila model for retinal degeneration

  2007cited by this paper
• Rheb-TOR signaling promotes protein synthesis, but not glucose or amino acid import, in Drosophila

  2007cited by this paper
• Gravitaxis in Drosophila melanogaster: a forward genetic screen

  2006cited by this paper
• Specific age related signatures in Drosophila body parts transcriptome

  2006cited by this paper
• Robustness of Neural Coding in Drosophila Photoreceptors in the Absence of Slow Delayed Rectifier K+ Channels

  2006cited by this paper
• Differential decline in behavioral performance of Drosophila melanogaster with age.

  2006cited by this paper
• Age-dependent changes of gene expression in the Drosophila head.

  2005cited by this paper
• Functional senescence in Drosophila melanogaster.

  2005cited by this paper
• Isolation of mRNA from specific tissues of Drosophila by mRNA tagging

  2005cited by this paper
• The Multiple Functions of Cysteine-String Protein Analyzed at Drosophila Nerve Terminals

  2005cited by this paper
• Gene regulation and DNA damage in the ageing human brain

  2004cited by this paper
• Distinct roles for Argonaute proteins in small RNA-directed RNA cleavage pathways.

  2004cited by this paper
• Identification of alternative splicing regulators by RNA interference in Drosophila.

  2004cited by this paper
• Gene expression variation in the adult human retina.

  2004cited by this paper
• Structure–function analysis of rods and cones in juvenile, adult, and aged C57BL/6 and Balb/c mice

  2003cited by this paper
• Neural Dysfunction and Neurodegeneration inDrosophila Na+/K+ ATPase Alpha Subunit Mutants

  2003cited by this paper
• The aging of the retina.

  2003cited by this paper
• Shaker K+ channels contribute early nonlinear amplification to the light response in Drosophila photoreceptors.

  2003cited by this paper
• Mitochondrial and Cytoplasmic Thioredoxin Reductase Variants Encoded by a Single Drosophila Gene Are Both Essential for Viability*

  2002cited by this paper
• Control of poly(A) polymerase level is essential to cytoplasmic polyadenylation and early development in Drosophila

  2002cited by this paper
• Photoreceptor topography in ageing and age-related maculopathy

  2001cited by this paper
• Profile of the genes expressed in the human peripheral retina, macula, and retinal pigment epithelium determined through serial analysis of gene expression (SAGE)

  2001cited by this paper
• Biomechanics: Turning the key on Drosophila audition

  2001cited by this paper
• Isolation and genetic characterisation of the Drosophila homologue of (SCE)REV3, encoding the catalytic subunit of DNA polymerase zeta.

  2001cited by this paper
• BIOINFORMATICS APPLICATIONS NOTE

  2001cited by this paper
• Pre-Messenger RNA Processing Factors in the Drosophila Genome

  2000cited by this paper
• Genes Encoding Drosophila melanogaster RNA Polymerase II General Transcription Factors

  2000cited by this paper
• Roles of molecular chaperones in the nervous system.

  2000cited by this paper

• Broad Epigenetic Shifts in the Aging Drosophila Retina Contribute to Its Altered Diurnal Rhythmic Transcriptome

  2026influential citation
• Ribonuclease κ promotes longevity by preventing age-associated accumulation of circular RNA in stress granules.

  2026cites this paper
• Assessing transcriptomic signatures of aging: Testing an mRNA marker panel for forensic age estimation of blood samples.

  2025cites this paper
• Circular RNAs exhibit exceptional stability in the aging brain and serve as reliable age and experience indicators

  2025cites this paper
• An integrative systems-biology approach defines mechanisms of Alzheimer’s disease neurodegeneration

  2025cites this paper
• Broad epigenetic shifts in the aging Drosophila retina contribute to its altered rhythmic transcriptome

  2025influential citation
• Circular RNAs accumulate in aging human placental tissue and in stillbirth, leading to DNA damage and cellular senescence.

  2025cites this paper
• Effects of aging on gene expression networks in the Drosophila genetic reference panel

  2025cites this paper
• Biogenesis of circular RNAs in vitro and in vivo from the Drosophila Nk2.1/scarecrow gene

  2025cites this paper
• Loss of age-accumulated crh-1 circRNAs ameliorate amyloid β-induced toxicity in a C. elegans model for Alzheimer’s disease

  2024cites this paper
• Time is ticking faster for long genes in aging.

  2024cites this paper
• Biogenesis of circular RNAs in vitro and in vivo from the Drosophila Nk2.1/scarecrow gene

  2024cites this paper
• Noncoding RNA Regulation of Hormonal and Metabolic Systems in the Fruit Fly Drosophila

  2023cites this paper
• Regulatory mechanism of circular RNAs in neurodegenerative diseases

  2023cites this paper
• R-loops in neuronal aging

  2023cites this paper
• Going circular: history, present, and future of circRNAs in cancer

  2023cites this paper
• What do we mean by "aging"?: Questions and perspectives revealed by studies in Drosophila.

  2023cites this paper
• Genome-wide RNA polymerase stalling shapes the transcriptome during aging

  2023cites this paper
• Eye proteome of Drosophila melanogaster

  2023cites this paper
• Targeted RNAi screen identifies transcriptional mechanisms that prevent premature degeneration of adult photoreceptors

  2023cites this paper
• Proteome-wide quantitative analysis of redox cysteine availability in the Drosophila melanogaster eye reveals oxidation of phototransduction machinery during blue light exposure and age

  2023cites this paper
• The Potential Biological Roles of Circular RNAs in the Immune Systems of Insects to Pathogen Invasion

  2023cites this paper
• The Road Less Traveled: Uncovering the Convergence Toward Specific Pleiotropic Phenotypes in Aging

  2023cites this paper
• Eye proteome of Drosophila melanogaster

  2023cites this paper
• Aging Fly Cell Atlas Identifies Exhaustive Aging Features at Cellular Resolution

  2023cites this paper
• Establishing the contribution of active histone methylation marks to the aging transcriptional landscape of Drosophila photoreceptors

  2023cites this paper
• Establishing the contribution of active histone methylation marks to the aging transcriptional landscape of Drosophila photoreceptors

  2022cites this paper
• Aging and memory are altered by genetically manipulating lactate dehydrogenase in the neurons or glia of flies

  2022cites this paper
• Emerging roles of circRNAs in mice kidney with aging

  2022cites this paper
• Molecular and cytological profiling of biological aging of mouse cochlear inner and outer hair cells

  2022cites this paper
• Circular RNA as a Potential Biomarker for Forensic Age Prediction

  2022cites this paper
• Aging and Light Stress Result in Overlapping and Unique Gene Expression Changes in Photoreceptors

  2022cites this paper
• Proper control of R‐loop homeostasis is required for maintenance of gene expression and neuronal function during aging

  2022cites this paper
• Dietary restriction and the transcription factor clock delay eye aging to extend lifespan in Drosophila Melanogaster

  2022cites this paper
• The transcription factor Xrp1 is required for PERK-mediated antioxidant gene induction in Drosophila

  2021cites this paper
• Structural aspects of the aging invertebrate brain

  2021cites this paper
• Splicing alterations in healthy aging and disease

  2021cites this paper
• In vivo tissue-specific chromatin profiling in Drosophila melanogaster using GFP-tagged nuclei

  2021cites this paper
• The histone variant Sl_H2A.Z regulates carotenoid biosynthesis and gene expression during tomato fruit ripening

  2021cites this paper
• Drosophila fabp is a retinoid-inducible gene required for Rhodopsin-1 homeostasis and photoreceptor survival

  2021cites this paper
• Characterizing a gene expression toolkit for eye- and photoreceptor-specific expression in Drosophila

  2021cites this paper
• NOVA2 regulates neural circRNA biogenesis

  2021cites this paper
• Dietary restriction and clock delay eye aging to extend lifespan in D. melanogaster

  2021cites this paper
• Emerging functions of circular RNA in aging.

  2021cites this paper
• Aging of the Retina: Molecular and Metabolic Turbulences and Potential Interventions.

  2021cites this paper
• Quantitative Proteomic and Metabolomic Profiling Reveals Altered Mitochondrial Metabolism and Folate Biosynthesis Pathways in the Aging Drosophila Eye

  2021cites this paper
• The Emerging Role of Circ-SHPRH in Cancer

  2021cites this paper
• The Transcription Factor Xrp1 is Required for PERK- Mediated Antioxidant Gene Induction in Drosophila

  2021cites this paper
• The Clock:Cycle complex is a major transcriptional regulator of Drosophila photoreceptors that protects the eye from retinal degeneration and oxidative stress

  2021cites this paper
• The histone variant Sl_H2A.Z regulates carotenoid biosynthesis and gene expression during tomato fruit ripening

  2021cites this paper
• Transcriptome sequencing and screening of genes related to glucose availability in Schizosaccharomyces pombe by RNA-seq analysis

  2021cites this paper
• An Insulin-Sensitive Circular RNA that Regulates Lifespan in Drosophila

  2020cites this paper
• Biogenesis and Functions of Circular RNAs Come into Focus.

  2020cites this paper
• Drosophila fabp is required for light-dependent Rhodopsin-1 clearance and photoreceptor survival

  2020cites this paper
• Comparative transcriptome analyses of the Drosophila pupal eye

  2020cites this paper
• Circular RNA as a potential biomarker for forensic age prediction using multiple machine learning models: A preliminary study

  2020cites this paper
• Neural circular transcriptomes across mammalian species.

  2020cites this paper
• Transposable elements, circular RNAs and mitochondrial transcription in age-related genomic regulation

  2020cites this paper
• Aging mechanisms—A perspective mostly from Drosophila

  2020cites this paper
• The roles of cirRNA in the development of germ cells.

  2020cites this paper
• Dynamic transcriptome profiling exploring cold tolerance in forensically important blow fly, Aldrichina grahami (Diptera: Calliphoridae)

  2020cites this paper
• Comprehensive analysis of circular RNAs in pathological states: biogenesis, cellular regulation, and therapeutic relevance

  2019cites this paper
• RiboTag translatomic profiling of Drosophila oenocytes under aging and induced oxidative stress

  2019cites this paper
• CircRNAs and cancer: Biomarkers and master regulators.

  2019cites this paper
• Circular RNA involvement in aging: An emerging player with great potential.

  2019cites this paper
• Longevity‐related molecular pathways are subject to midlife “switch” in humans

  2019cites this paper
• Age-Dependent Changes in Transcription Factor FOXO Targeting in Female Drosophila

  2019cites this paper
• translatomic profiling of Drosophila oenocytes under aging and oxidative stress 1

  2018cites this paper
• Blue light induces a neuroprotective gene expression program in Drosophila photoreceptors

  2018cites this paper
• RiboTag translatomic profiling of Drosophila oenocytes under aging and oxidative stress

  2018cites this paper
• CircRNA accumulation: A new hallmark of aging?

  2018cites this paper
• Genetic mechanisms of the influence of light and phototransduction on Drosophila melanogaster lifespan

  2018cites this paper
• Gene Expression, Epigenetics and Ageing.

  2018cites this paper
• Aging and the clock: Perspective from flies to humans

  2018influential citation
• Identification and characterization of human ovary-derived circular RNAs and their potential roles in ovarian aging

  2018influential citation
• Annotation and functional clustering of circRNA expression in rhesus macaque brain during aging

  2018cites this paper
• Proper splicing contributes to visual function in the aging Drosophila eye

  2018cites this paper
• Transcriptome Profiling Identifies Multiplexin as a Target of SAGA Deubiquitinase Activity in Glia Required for Precise Axon Guidance During Drosophila Visual Development

  2016cites this paper
• Purdue e-Pubs Purdue e-Pubs

  year unknowninfluential citation