PUBLICATION

MicroRNA miR-29 controls a compensatory response to limit neuronal iron accumulation during adult life and aging

Authors
Ripa, R., Dolfi, L., Terrigno, M., Pandolfini, L., Savino, A., Arcucci, V., Groth, M., Terzibasi Tozzini, E., Baumgart, M., Cellerino, A.
ID
ZDB-PUB-171017-16
Date
2017
Source
BMC Biology   15: 9 (Journal)
Registered Authors
Cellerino, Alessandro
Keywords
none
MeSH Terms
  • Iron Regulatory Protein 2/genetics
  • Iron Regulatory Protein 2/metabolism
  • Aging/genetics*
  • Models, Biological
  • Animals
  • Brain/metabolism
  • RNA, Messenger/genetics
  • RNA, Messenger/metabolism
  • Neurons/metabolism*
  • Homeostasis/genetics
  • Iron/metabolism*
  • MicroRNAs/genetics
  • MicroRNAs/metabolism*
  • Zebrafish/genetics
  • Killifishes/genetics*
  • Killifishes/growth & development*
  • Up-Regulation/genetics
  • Base Sequence
  • Iron Overload/genetics
  • Iron Overload/metabolism
(all 20)
PubMed
28193224 Full text @ BMC Biol.
Abstract
Background A widespread modulation of gene expression occurs in the aging brain, but little is known as to the upstream drivers of these changes. MicroRNAs emerged as fine regulators of gene expression in many biological contexts and they are modulated by age. MicroRNAs may therefore be part of the upstream drivers of the global gene expression modulation correlated with aging and aging-related phenotypes.
Results Here, we show that microRNA-29 (miR-29) is induced during aging in short-lived turquoise killifish brain and genetic antagonism of its function induces a gene-expression signature typical of aging. Mechanicistically, we identified Ireb2 (a master gene for intracellular iron delivery that encodes for IRP2 protein), as a novel miR-29 target. MiR-29 is induced by iron loading and, in turn, it reduces IRP2 expression in vivo, therefore limiting intracellular iron delivery in neurons. Genetically modified fish with neuro-specific miR-29 deficiency exhibit increased levels of IRP2 and transferrin receptor, increased iron content, and oxidative stress.
Conclusions Our results demonstrate that age-dependent miR-29 upregulation is an adaptive mechanism that counteracts the expression of some aging-related phenotypes and its anti-aging activity is primarily exerted by regulating intracellular iron homeostasis limiting excessive iron-exposure in neurons.
Genes / Markers
Figures
Figure Gallery (3 images)
Show all Figures
Expression
No data available
Phenotype
No data available
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
zf2081TgTransgenic Insertion
    zf2082TgTransgenic Insertion
      1 - 2 of 2
      Show
      Human Disease / Model
      No data available
      Sequence Targeting Reagents
      No data available
      Fish
      No data available
      Antibodies
      Orthology
      Gene Orthology
      ireb2
      1 - 1 of 1
      Show
      Engineered Foreign Genes
      Marker Marker Type Name
      EGFPEFGEGFP
      1 - 1 of 1
      Show
      Mapping
      No data available
      Your Input Welcome
      We welcome your input and comments. Please use this form to recommend updates to the information in ZFIN. We appreciate as much detail as possible and references as appropriate. We will review your comments promptly.
      Citation
      Ripa, R., Dolfi, L., Terrigno, M., Pandolfini, L., Savino, A., Arcucci, V., Groth, M., Terzibasi Tozzini, E., Baumgart, M., Cellerino, A. (2017) MicroRNA miR-29 controls a compensatory response to limit neuronal iron accumulation during adult life and aging. BMC Biology. 15:9.