The RNA-binding protein SFPQ orchestrates an RNA regulon to promote axon viability

Nat Neurosci. 2016 May;19(5):690-696. doi: 10.1038/nn.4280. Epub 2016 Mar 28.

Abstract

To achieve accurate spatiotemporal patterns of gene expression, RNA-binding proteins (RBPs) guide nuclear processing, intracellular trafficking and local translation of target mRNAs. In neurons, RBPs direct transport of target mRNAs to sites of translation in remote axons and dendrites. However, it is not known whether an individual RBP coordinately regulates multiple mRNAs within these morphologically complex cells. Here we identify SFPQ (splicing factor, poly-glutamine rich) as an RBP that binds and regulates multiple mRNAs in dorsal root ganglion sensory neurons and thereby promotes neurotrophin-dependent axonal viability. SFPQ acts in nuclei, cytoplasm and axons to regulate functionally related mRNAs essential for axon survival. Notably, SFPQ is required for coassembly of LaminB2 (Lmnb2) and Bclw (Bcl2l2) mRNAs in RNA granules and for axonal trafficking of these mRNAs. Together these data demonstrate that SFPQ orchestrates spatial gene expression of a newly identified RNA regulon essential for axonal viability.

MeSH terms

  • Animals
  • Apoptosis Regulatory Proteins
  • Axonal Transport / physiology
  • Axons / physiology*
  • Cell Survival / physiology
  • Ganglia, Spinal / metabolism
  • Gene Knockdown Techniques
  • Lamin Type B / metabolism
  • Mice
  • Mice, Knockout
  • PTB-Associated Splicing Factor / genetics
  • PTB-Associated Splicing Factor / physiology*
  • Proteins / genetics
  • Proteins / metabolism
  • RNA / metabolism*
  • Regulon / physiology*
  • Sensory Receptor Cells / metabolism

Substances

  • Apoptosis Regulatory Proteins
  • Bcl2l2 protein, mouse
  • Lamin Type B
  • PTB-Associated Splicing Factor
  • Proteins
  • lamin B2
  • RNA