Neuronal RNA granules and their functions at the synapse

Certain neuronal mRNAs are transported to dendrites, where their local translation contributes to synaptic plasticity, learning and memory. Defects in RNA localization can have severe consequences for the function of cells as documented for human diseases including fragile X mental retardation, spinal muscular atrophy, and myotonic dystrophy. Transport of RNAs to dendrites and synapses is thought to occur in ribonucleoprotein particles (RNPs), however, little is known about the underlying components and their functions in mRNA localization. We propose to isolate functional RNA transport RNPs from rat neurons. Known particle components such as Staufen1, Staufen2, and Barentsz serve as molecular `handles` and as markers to unravel the molecular composition of these neuronal RNA granules. The functions of newly identified components, including previously known localization factors, as well as new factors and RNA cargoes, will be characterized in detail at the cellular and molecular level using a battery of in vivo and in vitro functional assays. We expect that this thorough analysis will greatly advance the mechanistic understanding of dendritic RNA localization and its contribution to learning and memory at the synapse.

Certain neuronal mRNAs are transported to dendrites, where their local translation contributes to synaptic plasticity, learning and memory. Defects in RNA localization can have severe consequences for the function of cells as documented for human diseases including fragile X mental retardation, spinal muscular atrophy, and myotonic dystrophy. Transport of RNAs to dendrites and synapses is thought to occur in ribonucleoprotein particles (RNPs), however, little is known about the underlying components and their functions in mRNA localization. We propose to isolate functional RNA transport RNPs from rat neurons. Known particle components such as Staufen1, Staufen2, and Barentsz serve as molecular "handles" and as markers to unravel the molecular composition of these neuronal RNA granules. The functions of newly identified components, including previously known localization factors, as well as new factors and RNA cargoes, will be characterized in detail at the cellular and molecular level using a battery of in vivo and in vitro functional assays. We expect that this thorough analysis will greatly advance the mechanistic understanding of dendritic RNA localization and its contribution to learning and memory at the synapse.