RRC ID 45820
Author Norris AD, Gao S, Norris ML, Ray D, Ramani AK, Fraser AG, Morris Q, Hughes TR, Zhen M, Calarco JA.
Title A pair of RNA-binding proteins controls networks of splicing events contributing to specialization of neural cell types.
Journal Mol Cell
Abstract Alternative splicing is important for the development and function of the nervous system, but little is known about the differences in alternative splicing between distinct types of neurons. Furthermore, the factors that control cell-type-specific splicing and the physiological roles of these alternative isoforms are unclear. By monitoring alternative splicing at single-cell resolution in Caenorhabditis elegans, we demonstrate that splicing patterns in different neurons are often distinct and highly regulated. We identify two conserved RNA-binding proteins, UNC-75/CELF and EXC-7/Hu/ELAV, which regulate overlapping networks of splicing events in GABAergic and cholinergic neurons. We use the UNC-75 exon network to discover regulators of synaptic transmission and to identify unique roles for isoforms of UNC-64/Syntaxin, a protein required for synaptic vesicle fusion. Our results indicate that combinatorial regulation of alternative splicing in distinct neurons provides a mechanism to specialize metazoan nervous systems.
Volume 54(6)
Pages 946-959
Published 2014-6-19
DOI 10.1016/j.molcel.2014.05.004
PII S1097-2765(14)00398-0
PMID 24910101
PMC PMC4096705
MeSH Alternative Splicing / genetics* Animals Caenorhabditis elegans / genetics* Caenorhabditis elegans Proteins / genetics* Caenorhabditis elegans Proteins / physiology* Cholinergic Neurons / cytology* Cholinergic Neurons / metabolism GABAergic Neurons / cytology* GABAergic Neurons / metabolism Mutation Nervous System / embryology Nervous System / growth & development Protein Isoforms / genetics RNA-Binding Proteins / genetics RNA-Binding Proteins / physiology* Synaptic Transmission / genetics* Synaptic Transmission / physiology Synaptic Vesicles / metabolism Syntaxin 1 / genetics*
IF 15.584
Times Cited 33
WOS Category BIOCHEMISTRY & MOLECULAR BIOLOGY CELL BIOLOGY
Resource
C.elegans tm4167 tm2423 tm3303 tm3444