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Science. 2016 May 20;352(6288):982-6. doi: 10.1126/science.aaf2397. Epub 2016 May 12.

Control of neuronal synapse specification by a highly dedicated alternative splicing program.

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Biozentrum, University of Basel Klingelbergstrasse 50-70, 4056 Basel, Switzerland.
Biozentrum, University of Basel Klingelbergstrasse 50-70, 4056 Basel, Switzerland


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.

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