Blue light induces a neuroprotective gene expression program in Drosophila photoreceptors DOI Creative Commons
Hana Hall, Jingqun Ma, Sudhanshu Shekhar

et al.

BMC Neuroscience, Journal Year: 2018, Volume and Issue: 19(1)

Published: July 20, 2018

Light exposure induces oxidative stress, which contributes to ocular diseases of aging. Blue light provides a model for light-induced lipid peroxidation and retinal degeneration in Drosophila melanogaster. In contrast mature adults, undergo when exposed prolonged blue light, newly-eclosed flies are resistant degeneration. Here, we sought characterize the gene expression programs induced by different ages identify neuroprotective pathways utilized photoreceptors cope with stress. To changes exposure, profiled nuclear transcriptome from one- six-day-old compared these dark controls. Flies were 3 h increases levels reactive oxygen species but does not cause We identified substantial response only flies. flies, program that included upregulation stress downregulation genes involved response, calcium influx ion transport. An intact phototransduction pathway required upregulation, downregulation, suggesting distinct mediate light-associated transcriptional response. Our data demonstrate under phototoxic conditions, upregulate simultaneously, downregulate components, transporters, channels. Together, this both counteracts resulting ameliorates influx. Thus, can withstand up without undergoing Developmental transitions during first week adult life lead an altered includes reduced maintain redox homeostasis, reducing capacity longer periods (8 h) exposure. provide insight into regulatory mechanisms enable

Language: Английский

CircRNAs and cancer: Biomarkers and master regulators DOI
Esther Arnaiz, Carla Solé, Lorea Manterola

et al.

Seminars in Cancer Biology, Journal Year: 2018, Volume and Issue: 58, P. 90 - 99

Published: Dec. 11, 2018

Language: Английский

Citations

358
Biogenesis and Functions of Circular RNAs Come into Focus DOI

Mei‐Sheng Xiao,

Yuxi Ai, Jeremy E. Wilusz

et al.

Trends in Cell Biology, Journal Year: 2020, Volume and Issue: 30(3), P. 226 - 240

Published: Jan. 20, 2020

Language: Английский

Citations

279
Going circular: history, present, and future of circRNAs in cancer DOI Creative Commons
Giuseppina Pisignano, David C. Michael, Tanvi H. Visal

et al.

Oncogene, Journal Year: 2023, Volume and Issue: 42(38), P. 2783 - 2800

Published: Aug. 16, 2023

Abstract To date, thousands of highly abundant and conserved single-stranded RNA molecules shaped into ring structures (circRNAs) have been identified. CircRNAs are multifunctional that shown to regulate gene expression transcriptionally post-transcriptionally exhibit distinct tissue- development-specific patterns associated with a variety normal disease conditions, including cancer pathogenesis. Over the past years, due their intrinsic stability resistance ribonucleases, particular attention has drawn use as reliable diagnostic prognostic biomarkers in diagnosis, treatment, prevention. However, there some critical caveats utility clinic. Their circular shape limits annotation complete functional elucidation is lacking. This makes detection biomedical application still challenging. Herein, we review current knowledge circRNA biogenesis function, involvement tumorigenesis potential cancer-targeted therapy.

Language: Английский

Citations

102
Genome-wide RNA polymerase stalling shapes the transcriptome during aging DOI Creative Commons
Àkos Gyenis, Jiang Chang, Joris J. P. G. Demmers

et al.

Nature Genetics, Journal Year: 2023, Volume and Issue: 55(2), P. 268 - 279

Published: Jan. 19, 2023

Gene expression profiling has identified numerous processes altered in aging, but how these changes arise is largely unknown. Here we combined nascent RNA sequencing and polymerase II chromatin immunoprecipitation followed by to elucidate the underlying mechanisms triggering gene wild-type aged mice. We found that 2-year-old liver, 40% of elongating polymerases are stalled, lowering productive transcription skewing transcriptional output a gene-length-dependent fashion. demonstrate this stress caused endogenous DNA damage explains majority aging most mainly postmitotic organs, specifically affecting hallmark pathways such as nutrient sensing, autophagy, proteostasis, energy metabolism, immune function cellular resilience. Age-related evolutionary conserved from nematodes humans. Thus, accumulation stochastic during deteriorates basal transcription, which establishes age-related transcriptome causes dysfunction key pathways, disclosing functionally underlies major aspects normal aging.

Language: Английский

Citations

88
Aging Fly Cell Atlas identifies exhaustive aging features at cellular resolution DOI
Tzu‐Chiao Lu, Maria Brbić, Ye-Jin Park

et al.

Science, Journal Year: 2023, Volume and Issue: 380(6650)

Published: June 15, 2023

Aging is characterized by a decline in tissue function, but the underlying changes at cellular resolution across organism remain unclear. Here, we present Fly Cell Atlas, single-nucleus transcriptomic map of whole aging

Language: Английский

Citations

67
Loss of age-accumulated crh-1 circRNAs ameliorate amyloid β-induced toxicity in a C. elegans model for Alzheimer’s disease DOI Creative Commons
Hussam Z. Alshareef,

Thomas Ballinger,

Everett Rojas

et al.

Frontiers in Aging Neuroscience, Journal Year: 2025, Volume and Issue: 17

Published: March 24, 2025

Circular RNAs (circRNAs) are non-coding mostly derived from exons of protein-coding genes via a back-splicing process. The expression hundreds circRNAs accumulates during healthy aging and is associated with Alzheimer’s disease (AD), which characterized by the accumulation amyloid-beta (Aβ) proteins. In C. elegans , many were previously found to accumulate aging, loss age-accumulated CREB gene (circ- crh-1 ) increase mean lifespan. Here, we used study effects on age-related onset Aβ-toxicity. We that circ- mutations delayed Aβ-induced muscle paralysis lifespan phenotypes in transgenic strain expressing full-length human Aβ-peptide (Aβ 1–42 selectively cells (GMC101). Aβ phenotypic defects inhibition aggregate deposition, thus, genetic removal alleviated toxicity. Consistent detrimental role for AD, level elevated after induction whereas linear mRNA remains unchanged. Finally, observed mutants dependent col-49 collagen gene. Taken together, our results show an circRNA exerts protective toxicity, demonstrating utility studying AD its relationship aging.

Language: Английский

Citations

2
An Insulin-Sensitive Circular RNA that Regulates Lifespan in Drosophila DOI Creative Commons
Carina Marianne Weigelt,

Rohan Sehgal,

Luke S. Tain

et al.

Molecular Cell, Journal Year: 2020, Volume and Issue: 79(2), P. 268 - 279.e5

Published: June 26, 2020

Circular RNAs (circRNAs) are abundant and accumulate with age in neurons of diverse species. However, only few circRNAs have been functionally characterized, their role during aging has not addressed. Here, we use transcriptome profiling find that accumulation is slowed down long-lived insulin mutant flies. Next, characterize the vivo function a circRNA generated by sulfateless gene (circSfl), which consistently upregulated, particularly brain muscle, mutants. Strikingly, lifespan extension mutants dependent on circSfl, overexpression circSfl alone sufficient to extend lifespan. Moreover, translated into protein shares N terminus potentially some functions full-length Sfl encoded host gene. Our study demonstrates signaling affects global reveals an important vivo.

Language: Английский

Citations

109
Circular RNA involvement in aging: An emerging player with great potential DOI
Hongcai Cai, Yamin Li, Jean Damascene Niringiyumukiza

et al.

Mechanisms of Ageing and Development, Journal Year: 2018, Volume and Issue: 178, P. 16 - 24

Published: Dec. 1, 2018

Language: Английский

Citations

108
NOVA2 regulates neural circRNA biogenesis DOI Creative Commons

David Knupp,

Daphne Cooper,

Yuhki Saito

et al.

Nucleic Acids Research, Journal Year: 2021, Volume and Issue: 49(12), P. 6849 - 6862

Published: June 10, 2021

Abstract Circular RNAs (circRNAs) are highly expressed in the brain and their expression increases during neuronal differentiation. The factors regulating circRNAs developing mouse unknown. NOVA1 NOVA2 neural-enriched RNA-binding proteins with well-characterized roles alternative splicing. Profiling of from RNA-seq data revealed that global circRNA levels were reduced embryonic cortex Nova2 but not Nova1 knockout mice. Analysis isolated inhibitory excitatory cortical neurons lacking an even more dramatic reduction establishes a widespread role for enhancing biogenesis. To investigate cis-elements controlling NOVA2-regulation biogenesis, we generated backsplicing reporter based on Efnb2 gene. We found NOVA2-mediated circEfnb2 was impaired when YCAY clusters located flanking introns mutagenized. CLIP (cross-linking immunoprecipitation) additional analyses demonstrated importance binding sites both loci. is first protein identified to globally promote biogenesis brain.

Language: Английский

Citations

58
Molecular and cytological profiling of biological aging of mouse cochlear inner and outer hair cells DOI Creative Commons
Huizhan Liu, Kimberlee P. Giffen, Lei Chen

et al.

Cell Reports, Journal Year: 2022, Volume and Issue: 39(2), P. 110665 - 110665

Published: April 1, 2022

Age-related hearing loss (ARHL) negatively impacts quality of life in the elderly population. The prevalent cause ARHL is mechanosensitive cochlear hair cells (HCs). molecular and cellular mechanisms HC degeneration remain poorly understood. Using RNA-seq transcriptomic analyses inner outer HCs isolated from young aged mice, we show that aging associated with changes key processes, including transcription, DNA damage, autophagy, oxidative stress, as well genes related to specialization. At level, characterized by stereocilia, shrinkage soma, reduction mechanical properties, suggesting functional decline mechanotransduction amplification precedes contributes ARHL. Our study reveals cytological profiles identifies such Sod1, Sirt6, Jund, Cbx3 biomarkers potential therapeutic targets for ameliorating

Language: Английский

Citations

58