Cytoplasmic pool of spliceosome protein SNRNP70 regulates the axonal transcriptome and development of motor connectivity

Regulation of pre-mRNA splicing and polyadenylation plays a profound role in neurons by diversifying the proteome and modulating gene expression during development and in response to physiological cues. Although most pre-mRNA processing reactions are thought to occur in the nucleus, numerous splicing regulators are also found in neurites. Here, we show that U1-70K/SNRNP70, a major spliceosomal component, localizes in RNA-associated granules in axons. We identify the cytoplasmic pool of SNRNP70 as an important regulator of motor axonal growth, nerve-dependent acetylcholine receptor (AChR) clustering and neuromuscular synaptogenesis, and present evidence suggesting that SNRNP70 may modulate transcriptome composition, independently of its nuclear activities. Our results point to an unexpected, yet essential, function of cytoplasmic SNRNP70 in neuromuscular development and indicate a likely role of splicing factors in local RNA metabolism during establishment and maintenance of neuronal connectivity.