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Trans-cellular regulation of synaptic properties by neuron-specific alternative splicing

ABSTRACT: Genome-wide mapping of ribosome-associated mRNAs to investigate cell type-specific loss of function of the nuclear RNA binding protein SLM2 in the mouse hippocampus

ORGANISM(S): Mus musculus

PROVIDER: GSE209870 | GEO | 2022/07/30

REPOSITORIES: GEO

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			Action	DRS
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	GSE209870_STAR_read_counts_sR.tdl.txt.gz	Txt

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Trans-cellular control of synapse properties by a cell type-specific splicing regulator

Project description:The recognition of synaptic partners and specification of synaptic properties are fundamental for the function of neuronal circuits. 'Terminal selector' transcription factors coordinate the expression of terminal gene batteries that specify cell type-specific properties. Moreover, pan-neuronal alternative splicing regulators have been implicated in directing neuronal differentiation. However, the cellular logic of how splicing regulators instruct specific synaptic properties remains poorly understood. Here, we combine genome-wide mapping of mRNA targets and cell type-specific loss-of-function studies to uncover the contribution of the nuclear RNA binding protein SLM2 to hippocampal synapse specification. We find that SLM2 preferentially binds and regulates alternative splicing of transcripts encoding synaptic proteins, thereby generating cell type-specific isoforms. In the absence of SLM2, cell type-specification, differentiation, and viability are unaltered and neuronal populations exhibit normal intrinsic properties. By contrast, cell type-specific loss of SLM2 results in highly selective, non-cell autonomous synaptic phenotypes, altered synaptic transmission, and associated defects in a hippocampus-dependent memory task. Thus, alternative splicing provides a critical layer of gene regulation that instructs specification of neuronal connectivity in a trans-synaptic manner.

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Trans-cellular regulation of synaptic properties by neuron-specific alternative splicing

Project description:Trans-cellular regulation of synaptic properties by neuron-specific alternative splicing

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