ArticleNature communications2015
Alternative splicing of Drosophila Nmnat functions as a switch to enhance neuroprotection under stress.
Article in Nature communications, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 49 citations in OpenAlex.
- Elevated heat shock proteins in bipolar disorder patients with hypothalamic pituitary adrenal axis dysfunction.Medicine · 2018Trial
- Nicotinamide Mononucleotide Adenylyltransferase 1 and NADMetabolites · 2026Review
- MicroRNA-Mediated Obstruction of Stem-loop Alternative Splicing (MIMOSAS) regulates long-range alternative splicing in Drosophila.Nucleic acids research · 2026Article
- The Roles of Moonlighting Nicotinamide Mononucleotide Adenylyl Transferases in Cell Physiology.International journal of molecular sciences · 2025Review
- Climate change-induced stress in the honey beeFrontiers in physiology · 2025Review
- Loss-of-function approach using mouse retinal explants showed pivotal roles of Nmnat2 in early and middle stages of retinal development.Molecular biology of the cell · 2023Article
- The NADeLife · 2022Article
- Human Nmnat1 Promotes Autophagic Clearance of Amyloid Plaques in aFrontiers in aging neuroscience · 2022Article
- Article
- Presynaptic accumulation of α-synuclein causes synaptopathy and progressive neurodegeneration inBrain communications · 2021Article
- Exposure to Aerosolized Algal Toxins in South Florida Increases Short- and Long-Term Health Risk inToxins · 2020Article
- Article
- Genome-Wide Characterization of Alternative Splicing Events and Their Responses to Cold Stress in Tilapia.Frontiers in genetics · 2020Article
- Severe biallelic loss-of-function mutations in nicotinamide mononucleotide adenylyltransferase 2 (NMNAT2) in two fetuses with fetal akinesia deformation sequence.Experimental neurology · 2019Article
- MicroRNA miR-1002 Enhances NMNAT-Mediated Stress Response by Modulating Alternative Splicing.iScience · 2019Article
- Nmnat restores neuronal integrity by neutralizing mutant Huntingtin aggregate-induced progressive toxicity.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Review
- Subcellular compartmentalization of NADPharmacology & therapeutics · 2019Review
- Review
- PAM forms an atypical SCF ubiquitin ligase complex that ubiquitinates and degrades NMNAT2.The Journal of biological chemistry · 2018Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Nicotinamide mononucleotide adenylyltransferase (NMNAT) is a conserved enzyme in the NAD synthetic pathway. It has also been identified as an effective and versatile neuroprotective factor. However, it remains unclear how healthy neurons regulate the dual functions of NMNAT and achieve self-protection under stress. Here we show that Drosophila Nmnat (DmNmnat) is alternatively spliced into two mRNA variants, RA and RB, which translate to protein isoforms with divergent neuroprotective capacities against spinocerebellar ataxia 1-induced neurodegeneration. Isoform PA/PC translated from RA is nuclear-localized with minimal neuroprotective ability, and isoform PB/PD translated from RB is cytoplasmic and has robust neuroprotective capacity. Under stress, RB is preferably spliced in neurons to produce the neuroprotective PB/PD isoforms. Our results indicate that alternative splicing functions as a switch that regulates the expression of functionally distinct DmNmnat variants. Neurons respond to stress by driving the splicing switch to produce the neuroprotective variant and therefore achieve self-protection.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.