Cytoplasmic pool of U1 spliceosome protein SNRNP70 shapes the axonal transcriptome and regulates motor connectivity

Nikolas Nikolaou, Patricia Gordon, Fursham Hamid, Richard Taylor, Joshua Lloyd-Jones, Eugene Makeyev, Corinne Houart

Research output: Contribution to journalArticlepeer-review

Abstract

Regulation of pre-mRNA splicing and polyadenylation plays a profound role in neurons by diversifying the proteome and modulating gene expression in response to physiological cues. Although most of the pre-mRNA processing is thought to occur in the nucleus, numerous splicing regulators are also found in neurites. Here, we show that U1-70K/SNRNP70, a component of the major spliceosome, localizes in RNA-associated granules in zebrafish axons. We identify the extra-nuclear SNRNP70 as an important regulator of motor axonal growth, nerve-dependent acetylcholine receptor (AChR) clustering, and neuromuscular synaptogenesis. This cytoplasmic pool has a protective role for a limited number of transcripts regulating their abundance and trafficking inside axons. Moreover, non-nuclear SNRNP70 regulates splice variants of transcripts such as agrin, thereby controlling synapse formation. Our results point to an unexpected, yet essential, function of non-nuclear SNRNP70 in axonal development, indicating a role of spliceosome proteins in cytoplasmic RNA metabolism during neuronal connectivity.

Original languageEnglish
Pages (from-to)5099-5115.e8
JournalCurrent Biology
Volume32
Issue number23
DOIs
Publication statusPublished - 5 Dec 2022

Keywords

  • Z+agrn
  • alternative splicing
  • mRNA processing
  • mRNA stability
  • mRNA transport
  • motor neurons
  • neurodegenerative diseases
  • neuromuscular junction
  • ribonucleoprotein complexes
  • synaptic connectivity

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

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