The lin-4 gene controls fat accumulation and longevity in Caenorhabditis elegans

Int J Mol Sci. 2010;11(12):4814-25. doi: 10.3390/ijms11124814. Epub 2010 Nov 25.

Abstract

Previous studies have determined that lin-4, which was the first miRNA to be discovered, controls the timing of cell fate determination and life span in Caenorhabditis elegans. However, the mechanism of lin-4 involvement in these processes remains poorly understood. Fat storage is an essential aspect of the life cycle of organisms, and the function of lin-4 in fat accumulation is not clear. In this study, we showed that the fat content is reduced remarkably in C. elegans lin-4 mutants. Quantitative RT-PCR analysis revealed a considerable decrease in the levels of SBP-1 and OGA-1 mRNA in lin-4 mutants. We also showed that lin-4 mutants have a significantly shorter life span than wild-type worms. DCF assay experiments showed that the reactive oxygen species (ROS) levels increased and mitochondrial DNA (mtDNA) copy number decreased in loss-of-function lin-4 mutants. These mutants also showed attenuation of locomotion. Taken together, our findings suggest that lin-4 may play an important role in regulating fat accumulation and locomotion and that lin-4 may control the life span of C. elegans by mediating ROS production.

Keywords: Caenorhabditis elegans; fat accumulation; life span; lin-4; locomotion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / metabolism*
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism
  • DNA, Helminth / genetics
  • DNA, Helminth / metabolism
  • DNA, Mitochondrial / genetics
  • DNA, Mitochondrial / metabolism
  • Lipid Metabolism / physiology*
  • Longevity / physiology*
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Mutation
  • RNA, Helminth / genetics
  • RNA, Helminth / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Reactive Oxygen Species / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism

Substances

  • Caenorhabditis elegans Proteins
  • DNA, Helminth
  • DNA, Mitochondrial
  • MicroRNAs
  • RNA, Helminth
  • RNA, Messenger
  • Reactive Oxygen Species
  • SBP-1 protein, C elegans
  • Transcription Factors
  • lin-4 microRNA, C elegans