Age-associated changes in expression of small, noncoding RNAs, including microRNAs, in C. elegans.

Authors: Kato, Masaomi; Chen, Xiaowei; Inukai, Sachi; Zhao, Hongyu; Slack, Frank J
Year: 2011
Journal: RNA
Abstract: Small, noncoding RNAs (sncRNAs), including microRNAs (miRNAs), impact diverse biological events through the control of gene expression and genome stability. However, the role of these sncRNAs in aging remains largely unknown. To understand the contribution of sncRNAs to the aging process, we performed small RNA profiling by deep-sequencing over the course of Caenorhabditis elegans (C. elegans) aging. Many small RNAs, including a significant number of miRNAs, change their expression during aging in C. elegans. Further studies of miRNA expression changes under conditions that modify lifespan demonstrate the tight control of their expression during aging. Adult-specific loss of argonaute-like gene-1 (alg-1) activity, which is necessary for miRNA maturation and function, resulted in an abnormal lifespan, suggesting that miRNAs are, indeed, required in adulthood for normal aging. miRNA target prediction algorithms combined with transcriptome data and pathway enrichment analysis revealed likely targets of these age-associated miRNAs with known roles in aging, such as mitochondrial metabolism. Furthermore, a computational analysis of our deep-sequencing data identified additional age-associated sncRNAs, including miRNA star strands, novel miRNA candidates, and endo-siRNA sequences. We also show an increase of specific transfer RNA (tRNA) fragments during aging, which are known to be induced in response to stress in several organisms. This study suggests that sncRNAs including miRNAs contribute to lifespan regulation in C. elegans, and indicates new connections between aging, stress responses, and the small RNA world.


Created on Nov. 30, 2012, 12:36 p.m. and lastly updated on Nov. 30, 2012, 1:49 p.m.
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Species: Nematode

Experiments: 4
  • Lifespan assay 1. Confirmation of lifespan of spe-9(hc88) animals for library preparations
  • Lifespan assay 2. Lifespan of spe-9(hc88) animals exposed to RNAi against alg-1 only during adulthood
  • Lifespan assay 3. Lifespan of spe-9(hc88) animals at different temperatures
  • Lifespan assay 4. Lifespan of spe-9(hc88) animals exposed to RNAi of daf-2, daf-16 and hsf-1

  • Interventions:
  • alg-1 RNAi

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