Neuron-Specific IMP2 Overexpression by Synapsin Promoter-Driven AAV9: A Tool to Study Its Role in Axon Regeneration.

Sarah Blizard, Danielle Park, Natalie O'Toole, Sheeva Norooz, Martin Dela Torre, Young Son, Adam Holstein, Scarlett Austin, Joshua Harman, Samantha Haraszti, Daved Fared, Mei Xu

Research output: Contribution to journalArticlepeer-review

Abstract

Insulin-like growth factor II mRNA-binding protein (IMP) 2 is one of the three homologues (IMP1-3) that belong to a conserved family of mRNA-binding proteins. Its alternative splice product is aberrantly expressed in human hepatocellular carcinoma, and it is therefore identified as HCC. Previous works have indicated that IMP1/ZBP1 (zipcode binding protein) is critical in axon guidance and regeneration by regulating localization and translation of specific mRNAs. However, the role of IMP2 in the nervous system is largely unknown. We used the synapsin promoter-driven adeno-associated viral (AAV) 9 constructs for transgene expression both in vitro and in vivo. These viral vectors have proven to be effective to transduce the neuron-specific overexpression of IMP2 and HCC. Applying this viral vector in the injury-conditioned dorsal root ganglion (DRG) culture demonstrates that overexpression of IMP2 significantly inhibits axons regenerating from the neurons, whereas overexpression of HCC barely interrupts the process. Quantitative analysis of binding affinities of IMPs to β-actin mRNA reveals that it is closely associated with their roles in axon regeneration. Although IMPs share significant structural homology, the distinctive functions imply their different ability to localize specific mRNAs and to regulate the axonal translation.

Original languageAmerican English
JournalCells
Volume10
StatePublished - Oct 5 2021

Keywords

  • Animals
  • Axons
  • Carcinoma
  • Dependovirus
  • Ganglia
  • Gene Expression
  • Genetic
  • Hepatocellular
  • Humans
  • Inbred C57BL
  • Liver Neoplasms
  • Messenger
  • Mice
  • Nerve Regeneration
  • Neurons
  • Organ Specificity
  • Promoter Regions
  • RNA
  • RNA-Binding Proteins
  • Sciatic Nerve
  • Spinal
  • Synapsins
  • Transgenes

Disciplines

  • Medicine and Health Sciences

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