Life span extension via eIF4G inhibition is mediated by posttranscriptional remodeling of stress response gene expression in C. elegans.

Abstract

Reducing protein synthesis slows growth and development but can increase adult life span. We demonstrate that knockdown of eukaryotic translation initiation factor 4G (eIF4G), which is downregulated during starvation and dauer state, results in differential translation of genes important for growth and longevity in C. elegans. Genome-wide mRNA translation state analysis showed that inhibition of IFG-1, the C. elegans ortholog of eIF4G, results in a relative increase in ribosomal loading and translation of stress response genes. Some of these genes are required for life span extension when IFG-1 is inhibited. Furthermore, enhanced ribosomal loading of certain mRNAs upon IFG-1 inhibition was correlated with increased mRNA length. This association was supported by changes in the proteome assayed via quantitative mass spectrometry. Our results suggest that IFG-1 mediates the antagonistic effects on growth and somatic maintenance by regulating mRNA translation of particular mRNAs based, in part, on transcript length.

• Authors: Aric N Rogers, Di Chen, Gawain McColl, Gregg Czerwieniec, Krysta Felkey, Bradford W Gibson, Alan Hubbard, Simon Melov, Gordon J Lithgow, Pankaj Kapahi
• Journal: Cell metabolism (Cell Metab) Vol. 14 Issue 1 Pg. 55-66 (Jul 06 2011) ISSN: 1932-7420 [Electronic] United States
• PMID: 21723504 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier Inc. All rights reserved.

Chemical References

• 3' Untranslated Regions
• Caenorhabditis elegans Proteins
• Eukaryotic Initiation Factor-4G
• RNA, Messenger

Topics

• 3' Untranslated Regions
• Animals
• Caenorhabditis elegans (genetics)
• Caenorhabditis elegans Proteins (antagonists & inhibitors, genetics, metabolism)
• Eukaryotic Initiation Factor-4G (antagonists & inhibitors, genetics, metabolism)
• Gene Expression Regulation
• Longevity (genetics)
• Protein Biosynthesis
• RNA Interference
• RNA, Messenger (metabolism)
• Ribosomes (physiology)
• Stress, Physiological (genetics)