Functional and selective RNA interference in developing axons and growth cones. Academic Article uri icon

Overview

abstract

  • Developing axons and growth cones contain "local" mRNAs that are translated in response to various extracellular signaling molecules and have roles in several processes during axonal development, including axonal pathfinding, orientation of axons in chemotactic gradients, and in the regulation of neurotransmitter release. The molecular mechanisms that regulate mRNA translation within axons and growth cones are unknown. Here we show that proteins involved in RNA interference (RNAi), including argonaute-3 and argonaute-4, Dicer, and the fragile X mental retardation protein, are found in developing axons and growth cones. These proteins assemble into functional RNA-induced silencing complexes as transfection of small interfering RNAs selectively into distal axons results in distal axon-specific mRNA knock-down, without reducing transcript levels in proximal axons or associated diffusion of small interfering RNA into proximal axons or cell bodies. RhoA mRNA is localized to axons and growth cones, and intra-axonal translation of RhoA is required for growth cone collapse elicited by Semaphorin 3A (Sema3A), an axonal guidance cue. Selective knock-down of axonal RhoA mRNA abolishes Sema3A-dependent growth cone collapse. Our results demonstrate functional and potent RNAi in axons and identify an approach to spatially regulate mRNA transcripts at a subcellular level in neurons.

publication date

  • May 24, 2006

Research

keywords

  • Axons
  • Growth Cones
  • Nerve Tissue Proteins
  • Posterior Horn Cells

Identity

PubMed Central ID

  • PMC6675254

Scopus Document Identifier

  • 33745007605

Digital Object Identifier (DOI)

  • 10.1523/JNEUROSCI.5229-05.2006

PubMed ID

  • 16723529

Additional Document Info

volume

  • 26

issue

  • 21