COPI transport complexes bind to specific RNAs in neuronal cells

Our fundamental understanding of how several thousand diverse RNAs are recognized in the soma, sorted, packaged, transported and localized within the cell is fragmentary. The COPa and COPb proteins of the coatomer protein I (COPI) vesicle complex were reported to interact with specific RNAs and represent a candidate RNA sorting and transport system. To determine the RNA-binding profile of Golgi-derived COPI in neuronal cells, we performed formaldehyde-linked RNA immunoprecipitation, followed by high-throughput sequencing, a process we term FLRIP-Seq (FLRIP, formaldehyde-cross-linked immunoprecipitation). We demonstrate that COPa co-immunoprecipitates a specific set of RNAs that are enriched in G-quadruplex motifs and fragile X mental retardation protein-associated RNAs and that encode factors that predominantly localize to the plasma membrane and cytoskeleton and function within signaling pathways. These data support the novel function of COPI in inter-compartmental trafficking of RNA.