Experience-dependent translational state defined by cell type-specific ribosome profiling

Experience-dependent neuronal activity regulates the translation of mRNA, supporting memory formation. We have developed a new method termed translating ribosome affinity purification and ribosome profiling (TRiP) which allows us to determine cell type-specific ribosome occupancy of mRNA with nucleotide resolution. Using TRiP we show that a memory-inducing experience creates a distinct translational state in mouse CA1 pyramidal cells. The experience-dependent translation state is characterized by enhanced translation of protein-coding open reading frames (ORFs) including numerous components of the actin cytoskeleton and calcium/calmodulin binding proteins, and by decreased translation of a defined subset of genes containing upstream ORFs (uORFs). Using animals heterozygous for an unphosphorylatable allele of the eukaryotic translation initiation factor 2α (eIF2α), we show that dephosphorylation of eIF2α contributes significantly to the experience-dependent translation state. These observations demonstrate that TRiP is a valuable methodology for studying physiologically relevant changes in translational state in genetically defined cell types.

• Publication year

  2017

• Venue

  bioRxiv

• Publication date

  2017-08-01

• Fields of study

  Biology

• Identifiers
  DOI 10.1101/169425
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar

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• No concepts are published for this paper.

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