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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
PubMed

Insights

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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