ArticleNature aging2022
Decreased spliceosome fidelity and egl-8 intron retention inhibit mTORC1 signaling to promote longevity.
Article in Nature aging, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
25 citing papers in PubMed, 33 citations in OpenAlex.
- Vitamin BNature communications · 2026Article
- Phospholipase Cβ regulates negative associative memory through calcium dependent and independent mechanisms.The Journal of biological chemistry · 2026Article
- Phosphatidylinositol transfer protein-1 integrates insulin/IGF-1 and TOR signaling to negatively regulate lifespan and healthspan in Caenorhabditis elegans.Journal of biomedical science · 2026Article
- Review
- The Function of Poly (U) Binding Splicing Factor 60 (PUF60) in Disease Regulation.Anti-cancer agents in medicinal chemistry · 2026Review
- mTOR signaling networks: mechanistic insights and translational frontiers in disease therapeutics.Signal transduction and targeted therapy · 2025Review
- Article
- EIciRNAs in focus: current understanding and future perspectives.RNA biology · 2025Review
- Genome-wide modulation of alternative splicing by a predicted alpha helix in U2AF2.Nucleic acids research · 2025Article
- Vitamin BResearch square · 2025Article
- Article
- Transcript diversity in aging: cryptic transcription and splicing.Medical review (2021) · 2025Review
- The tumor suppressor CYLD acts as a deubiquitinase for mTOR to constrain its activity.bioRxiv : the preprint server for biology · 2025Article
- Intron Retention: A Reemerging Paradigm in RNA Biology and Post-Transcriptional Gene Regulation.Genes · 2025Review
- Regulation of transcriptome plasticity by mTOR signaling pathway.Experimental & molecular medicine · 2025Review
- Systematic identification of exercise-induced anti-aging processes involving intron retention.The journals of gerontology. Series A, Biological sciences and medical sciences · 2025Article
- Article
- Hyperactivation of mTORC1 by an endogenousmicroPublication biology · 2025Article
- Nutrient control of growth and metabolism through mTORC1 regulation of mRNA splicing.Molecular cell · 2024Article
- Quantitative proteomics of patient fibroblasts reveal biomarkers and diagnostic signatures of mitochondrial disease.JCI insight · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Changes in splicing fidelity are associated with loss of homeostasis and aging, yet only a handful of splicing factors have been shown to be causally required to promote longevity, and the underlying mechanisms and downstream targets in these paradigms remain elusive. Surprisingly, we found a hypomorphic mutation within ribonucleoprotein RNP-6/poly(U)-binding factor 60 kDa (PUF60), a spliceosome component promoting weak 3'-splice site recognition, which causes aberrant splicing, elevates stress responses and enhances longevity in Caenorhabditis elegans. Through genetic suppressor screens, we identify a gain-of-function mutation within rbm-39, an RNP-6-interacting splicing factor, which increases nuclear speckle formation, alleviates splicing defects and curtails longevity caused by rnp-6 mutation. By leveraging the splicing changes induced by RNP-6/RBM-39 activities, we uncover intron retention in egl-8/phospholipase C β4 (PLCB4) as a key splicing target prolonging life. Genetic and biochemical evidence show that neuronal RNP-6/EGL-8 downregulates mammalian target of rapamycin complex 1 (mTORC1) signaling to control organismal lifespan. In mammalian cells, PUF60 downregulation also potently and specifically inhibits mTORC1 signaling. Altogether, our results reveal that splicing fidelity modulates lifespan through mTOR signaling.
Indexed as
Identifiers
What OpenQuestion holds
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.