title: Control of neuronal synapse specification by a highly dedicated alternative splicing program.
abstract: Alternative RNA splicing represents a central mechanism for expanding the coding power of genomes. Individual RNA-binding proteins can control alternative splicing choices in hundreds of RNA transcripts, thereby tuning amounts and functions of large numbers of cellular proteins. We found that the RNA-binding protein SLM2 is essential for functional specification of glutamatergic synapses in the mouse hippocampus. Genome-wide mapping revealed a markedly selective SLM2-dependent splicing program primarily consisting of only a few target messenger RNAs that encode synaptic proteins. Genetic correction of a single SLM2-dependent target exon in the synaptic recognition molecule neurexin-1 was sufficient to rescue synaptic plasticity and behavioral defects in Slm2 knockout mice. These findings uncover a highly selective alternative splicing program that specifies synaptic properties in the central nervous system.
authors.affiliation: Biozentrum, University of Basel Klingelbergstrasse 50-70, 4056 Basel, Switzerland.
authors.forename: Lisa
authors.initials: L
authors.lastname: Traunmüller
authors.affiliation: Biozentrum, University of Basel Klingelbergstrasse 50-70, 4056 Basel, Switzerland.
authors.forename: Andrea M
authors.initials: AM
authors.lastname: Gomez
authors.affiliation: Biozentrum, University of Basel Klingelbergstrasse 50-70, 4056 Basel, Switzerland.
authors.forename: Thi-Minh
authors.initials: TM
authors.lastname: Nguyen
authors.affiliation: Biozentrum, University of Basel Klingelbergstrasse 50-70, 4056 Basel, Switzerland peter.scheiffele@unibas.ch.
authors.forename: Peter
authors.initials: P
authors.lastname: Scheiffele
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D001522:Behavior, Animal; D002135:Calcium-Binding Proteins; D005091:Exons; D055106:Genome-Wide Association Study; D018698:Glutamic Acid / Q000502:physiology*; D006624:Hippocampus / Q000166:cytology / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D019006:Neural Cell Adhesion Molecules / Q000235:genetics / Q000502:physiology; D009473:Neuronal Plasticity / Q000235:genetics / Q000502:physiology; D009474:Neurons / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D017384:Sequence Deletion; D013569:Synapses / Q000502:physiology*; D009435:Synaptic Transmission / Q000235:genetics / Q000502:physiology
chemical_list: D002135:Calcium-Binding Proteins; C486528:Khdrbs3 protein, mouse; D019006:Neural Cell Adhesion Molecules; C527193:Nrxn1 protein, mouse; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D018698:Glutamic Acid