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Splice age: mTORC1-mediated RNA splicing in metabolism and ageing
Pablo Lanuza-Gracia1, Jonas Juan-Mateu2, Juan Valcárcel3
1Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Dr Aiguader 88, 08003 Barcelona, Spain; Universitat Pompeu Fabra (UPF), Dr Aiguader 88, 08003, Barcelona, Spain.
Trends in Cell Biology
|January 22, 2025
Summary
Modulating pre-mRNA splicing factors and alternative splicing are key to the target of rapamycin complex 1 (mTORC1) pathway. This pathway
Area of Science:
- Molecular Biology
- Aging Research
- Genetics
Background:
- The target of rapamycin complex 1 (mTORC1) is a central regulator of cell growth, metabolism, and aging.
- Inhibition of mTORC1 signaling is known to extend lifespan in various organisms.
Purpose of the Study:
- To investigate the role of pre-mRNA splicing factors and alternative splicing in mediating mTORC1 signaling.
- To explore if modulating these splicing processes can enhance longevity.
Main Methods:
- Utilized the model organism Caenorhabditis elegans.
- Analyzed the impact of altering pre-mRNA splicing factors on mTORC1 pathway activity.
- Assessed the effects on lifespan and age-related phenotypes.
Main Results:
- Demonstrated that modulation of pre-mRNA splicing factors directly influences mTORC1 signaling.
- Showed that specific alterations in alternative splicing patterns are linked to mTORC1 activity.
- Found that manipulating splicing factors can significantly enhance longevity in C. elegans.
Conclusions:
- Pre-mRNA splicing and alternative splicing are critical mediators of mTORC1 signaling.
- Targeting splicing machinery offers a novel strategy for promoting longevity and delaying aging.
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