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Authors: Mukhopadhyay, Arnab
Tabrez, Syed Shamsh
Sharma, Ravi Datta
Jain, Vaibhav
Siddiqui, Atif Ahmed
Title: Differential alternative splicing coupled to nonsense-mediated decay of mRNA ensures dietary restriction-induced longevity
Publisher: Springer Nature
Publication Date: Aug-2017
Abstract: Alternative splicing (AS) coupled to nonsense-mediated decay (AS-NMD) is a conserved mechanism for post-transcriptional gene regulation. Here we show that, during dietary restriction (DR), AS is enhanced in Caenorhabditis elegans and mice. A splicing mediator hrpu-1 regulates a significant part of these AS events in C. elegans; knocking it down suppresses DR-mediated longevity. Concurrently, due to increased AS, NMD pathway genes are upregulated and knocking down UPF1 homologue smg-2 suppresses DR lifespan. Knockdown of NMD during DR significantly increases the inclusion of PTC-containing introns and the lengths of the 3′UTRs. Finally, we demonstrate that PHA-4/FOXA transcriptionally regulates the AS-NMD genes. Our study suggests that DR uses AS to amplify the proteome, supporting physiological remodelling required for enhanced longevity. This increases the dependence on NMD, but also helps fine-tune the expression of metabolic and splicing mediators. AS-NMD may thus provide an energetically favourable level of dynamic gene expression control during dietary restriction.
Appears in Collections:Molecular Aging, Publications

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