Two neuronal, nuclear-localized RNA binding proteins involved in synaptic transmission

Curr Biol. 2003 Aug 5;13(15):1317-23. doi: 10.1016/s0960-9822(03)00532-3.

Abstract

While there is evidence that distinct protein isoforms resulting from alternative pre-mRNA splicing play critical roles in neuronal development and function, little is known about molecules regulating alternative splicing in the nervous system. Using Caenorhabditis elegans as a model for studying neuron/target communication, we report that unc-75 mutant animals display neuroanatomical and behavioral defects indicative of a role in modulating GABAergic and cholinergic neurotransmission but not neuronal development. We show that unc-75 encodes an RRM domain-containing RNA binding protein that is exclusively expressed in the nervous system and neurosecretory gland cells. UNC-75 protein, as well as a subset of related C. elegans RRM proteins, localizes to dynamic nuclear speckles; this localization pattern supports a role for the protein in pre-mRNA splicing. We found that human orthologs of UNC-75, whose splicing activity has recently been documented in vitro, are expressed nearly exclusively in brain and when expressed in C. elegans, rescue unc-75 mutant phenotypes and localize to subnuclear puncta. Furthermore, we report that the subnuclear-localized EXC-7 protein, the C. elegans ortholog of the neuron-restricted Drosophila ELAV splicing factor, acts in parallel to UNC-75 to also affect cholinergic synaptic transmission. In conclusion, we identified a new neuronal, putative pre-mRNA splicing factor, UNC-75, and show that UNC-75, as well as the C. elegans homolog of ELAV, is required for the fine tuning of synaptic transmission. These findings thus provide a novel molecular link between pre-mRNA splicing and presynaptic function.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Base Sequence
  • Caenorhabditis elegans / physiology*
  • Caenorhabditis elegans Proteins / metabolism*
  • Chromosome Mapping
  • Gene Expression Profiling
  • Molecular Sequence Data
  • Motor Neurons / cytology
  • Phylogeny
  • RNA-Binding Proteins / genetics*
  • RNA-Binding Proteins / metabolism*
  • Synaptic Transmission / genetics
  • Synaptic Transmission / physiology*

Substances

  • Caenorhabditis elegans Proteins
  • EXC-7 protein, C elegans
  • RNA-Binding Proteins

Associated data

  • GENBANK/AY342388